PMID- 26602021 OWN - NLM STAT- MEDLINE DA - 20151125 DCOM- 20160311 IS - 1873-5835 (Electronic) IS - 0145-2126 (Linking) VI - 39 IP - 12 DP - 2015 Dec TI - Hope and hype surrounding circulating microRNA as potential next generation AML biomarkers. PG - 1309-11 LID - 10.1016/j.leukres.2015.09.018 [doi] LID - S0145-2126(15)30389-1 [pii] FAU - Abdelhamed, Sherif AU - Abdelhamed S AD - Department of Pediatrics, Portland, OR, United States; Pape Family Pediatric Research Institute, Portland, OR, United States; OHSU-Knight Cancer Institute, Portland, OR, United States; Oregon Health & Science University, Portland, OR, United States. FAU - Kurre, Peter AU - Kurre P AD - Department of Pediatrics, Portland, OR, United States; Pape Family Pediatric Research Institute, Portland, OR, United States; OHSU-Knight Cancer Institute, Portland, OR, United States; Oregon Health & Science University, Portland, OR, United States. Electronic address: kurrepe@ohsu.edu. LA - eng PT - Comment PT - Editorial DEP - 20150921 PL - England TA - Leuk Res JT - Leukemia research JID - 7706787 RN - 0 (MicroRNAs) RN - 0 (RNA, Neoplasm) SB - IM CON - Leuk Res. 2015 Dec;39(12):1389-95. PMID: 26340914 MH - Antineoplastic Combined Chemotherapy Protocols/*pharmacology MH - Female MH - Gene Expression Regulation, Leukemic/*drug effects MH - Humans MH - Leukemia, Myeloid, Acute/*drug therapy MH - Male MH - MicroRNAs/*blood MH - RNA, Neoplasm/*blood MH - *Transcriptome EDAT- 2015/11/26 06:00 MHDA- 2016/03/12 06:00 CRDT- 2015/11/26 06:00 PHST- 2015/09/14 [received] PHST- 2015/09/17 [accepted] PHST- 2015/09/21 [aheadofprint] AID - S0145-2126(15)30389-1 [pii] AID - 10.1016/j.leukres.2015.09.018 [doi] PST - ppublish SO - Leuk Res. 2015 Dec;39(12):1309-11. doi: 10.1016/j.leukres.2015.09.018. Epub 2015 Sep 21. PMID- 26585803 OWN - NLM STAT- MEDLINE DA - 20151120 DCOM- 20160304 IS - 1528-0020 (Electronic) IS - 0006-4971 (Linking) VI - 126 IP - 21 DP - 2015 Nov 19 TI - Cytopenias + mutations - dysplasia = what? PG - 2349-51 LID - 10.1182/blood-2015-10-672659 [doi] FAU - Steensma, David P AU - Steensma DP AUID- ORCID: http://orcid.org/0000-0001-5130-9284 AD - HARVARD MEDICAL SCHOOL. LA - eng PT - Comment PT - Journal Article PL - United States TA - Blood JT - Blood JID - 7603509 SB - AIM SB - IM CON - Blood. 2015 Nov 19;126(21):2362-5. PMID: 26392596 CON - Blood. 2015 Nov 19;126(21):2355-61. PMID: 26429975 MH - *Alleles MH - *Chromosome Aberrations MH - Female MH - *Gene Frequency MH - Hematopoiesis/*genetics MH - Humans MH - Leukemia, Myeloid, Acute/*genetics/*mortality MH - Male MH - *Mutation MH - Myelodysplastic Syndromes/*genetics/*mortality EDAT- 2015/11/21 06:00 MHDA- 2016/03/05 06:00 CRDT- 2015/11/21 06:00 AID - 126/21/2349 [pii] AID - 10.1182/blood-2015-10-672659 [doi] PST - ppublish SO - Blood. 2015 Nov 19;126(21):2349-51. doi: 10.1182/blood-2015-10-672659. PMID- 26568194 OWN - NLM STAT- MEDLINE DA - 20151116 DCOM- 20160314 LR - 20160101 IS - 1460-2105 (Electronic) IS - 0027-8874 (Linking) VI - 108 IP - 2 DP - 2016 Feb TI - Hypomethylation of TET2 Target Genes Identifies a Curable Subset of Acute Myeloid Leukemia. LID - 10.1093/jnci/djv323 [doi] LID - djv323 [pii] AB - BACKGROUND: Acute myeloid leukemia (AML) is curable in a subset of cases. The DNA methylation regulator TET2 is frequently mutated in AML, and we hypothesized that studying TET2-specific differentially methylated CpGs (tet2-DMCs) improves AML classification. METHODS: We used bisulfite pyrosequencing to analyze the methylation status of four tet2-DMCs (SP140, MCCC1, EHMT1, and MTSS1) in a test group of 94 consecutive patients and a validation group of 92 consecutive patients treated with cytarabine-based chemotherapy. Data were analyzed with hierarchical clustering, Cox proportional hazards regression, and Kaplan-Meier analyses. All statistical tests were two-sided. RESULTS: In the test cohort, hierarchical clustering analysis identified low levels of tet2-DMC methylation in 31 of 94 (33%) cases, and these had markedly longer overall survival (median survival 72+ vs 14 months, P = .002). Similar results were seen in the validation cohort. tet2-DMC-low status was shown to be an independent predictor of overall survival (hazard ratio = 0.29, P = .0002). In The Cancer Genome Atlas (TCGA) dataset where DNA methylation was analyzed by a different platform, tet2-DMC-low methylation was also associated with improved outcome (median survival = 55 vs 15 months, P = .0003) and was a better predictor of survival than mutations in TET2, IDH1, or IDH2, individually or combined. CONCLUSIONS: Low levels of tet2-DMC methylation define a subgroup of AML that is highly curable and cannot be identified solely by genetic and cytogenetic analyses. CI - (c) The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com. FAU - Yamazaki, Jumpei AU - Yamazaki J AD - Fels Institute for Cancer Research and Molecular Biology, Temple University, Philadelphia, PA (JY, JJ, NJMR, MC, JPJI); Department of Leukemia (JY, RT, JJ, NJMR, SAP, SMK, FR, HMK, JPJI) and Department of Hematopathology (CEBR), The University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Taby, Rodolphe AU - Taby R AD - Fels Institute for Cancer Research and Molecular Biology, Temple University, Philadelphia, PA (JY, JJ, NJMR, MC, JPJI); Department of Leukemia (JY, RT, JJ, NJMR, SAP, SMK, FR, HMK, JPJI) and Department of Hematopathology (CEBR), The University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Jelinek, Jaroslav AU - Jelinek J AD - Fels Institute for Cancer Research and Molecular Biology, Temple University, Philadelphia, PA (JY, JJ, NJMR, MC, JPJI); Department of Leukemia (JY, RT, JJ, NJMR, SAP, SMK, FR, HMK, JPJI) and Department of Hematopathology (CEBR), The University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Raynal, Noel J M AU - Raynal NJ AD - Fels Institute for Cancer Research and Molecular Biology, Temple University, Philadelphia, PA (JY, JJ, NJMR, MC, JPJI); Department of Leukemia (JY, RT, JJ, NJMR, SAP, SMK, FR, HMK, JPJI) and Department of Hematopathology (CEBR), The University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Cesaroni, Matteo AU - Cesaroni M AD - Fels Institute for Cancer Research and Molecular Biology, Temple University, Philadelphia, PA (JY, JJ, NJMR, MC, JPJI); Department of Leukemia (JY, RT, JJ, NJMR, SAP, SMK, FR, HMK, JPJI) and Department of Hematopathology (CEBR), The University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Pierce, Sherry A AU - Pierce SA AD - Fels Institute for Cancer Research and Molecular Biology, Temple University, Philadelphia, PA (JY, JJ, NJMR, MC, JPJI); Department of Leukemia (JY, RT, JJ, NJMR, SAP, SMK, FR, HMK, JPJI) and Department of Hematopathology (CEBR), The University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Kornblau, Steven M AU - Kornblau SM AD - Fels Institute for Cancer Research and Molecular Biology, Temple University, Philadelphia, PA (JY, JJ, NJMR, MC, JPJI); Department of Leukemia (JY, RT, JJ, NJMR, SAP, SMK, FR, HMK, JPJI) and Department of Hematopathology (CEBR), The University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Bueso-Ramos, Carlos E AU - Bueso-Ramos CE AD - Fels Institute for Cancer Research and Molecular Biology, Temple University, Philadelphia, PA (JY, JJ, NJMR, MC, JPJI); Department of Leukemia (JY, RT, JJ, NJMR, SAP, SMK, FR, HMK, JPJI) and Department of Hematopathology (CEBR), The University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Ravandi, Farhad AU - Ravandi F AD - Fels Institute for Cancer Research and Molecular Biology, Temple University, Philadelphia, PA (JY, JJ, NJMR, MC, JPJI); Department of Leukemia (JY, RT, JJ, NJMR, SAP, SMK, FR, HMK, JPJI) and Department of Hematopathology (CEBR), The University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Kantarjian, Hagop M AU - Kantarjian HM AD - Fels Institute for Cancer Research and Molecular Biology, Temple University, Philadelphia, PA (JY, JJ, NJMR, MC, JPJI); Department of Leukemia (JY, RT, JJ, NJMR, SAP, SMK, FR, HMK, JPJI) and Department of Hematopathology (CEBR), The University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Issa, Jean-Pierre J AU - Issa JP AD - Fels Institute for Cancer Research and Molecular Biology, Temple University, Philadelphia, PA (JY, JJ, NJMR, MC, JPJI); Department of Leukemia (JY, RT, JJ, NJMR, SAP, SMK, FR, HMK, JPJI) and Department of Hematopathology (CEBR), The University of Texas MD Anderson Cancer Center, Houston, TX. jpissa@temple.edu. LA - eng GR - CA049639/CA/NCI NIH HHS/United States GR - CA100632/CA/NCI NIH HHS/United States GR - CA121104/CA/NCI NIH HHS/United States GR - P30 CA016672/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20151113 PL - United States TA - J Natl Cancer Inst JT - Journal of the National Cancer Institute JID - 7503089 RN - 0 (DNA, Neoplasm) RN - 0 (DNA-Binding Proteins) RN - 0 (Proto-Oncogene Proteins) RN - 0 (Sulfites) RN - 0 (TET2 protein, human) RN - OJ9787WBLU (hydrogen sulfite) SB - IM MH - Adult MH - Aged MH - CpG Islands/*genetics MH - *DNA Methylation MH - DNA, Neoplasm/*metabolism MH - DNA-Binding Proteins/*genetics MH - Female MH - Humans MH - Kaplan-Meier Estimate MH - Leukemia, Myeloid, Acute/*genetics/mortality MH - Male MH - Middle Aged MH - Odds Ratio MH - Predictive Value of Tests MH - Prognosis MH - Proto-Oncogene Proteins/*genetics MH - Sequence Analysis, DNA/methods MH - Sulfites EDAT- 2015/11/17 06:00 MHDA- 2016/03/15 06:00 CRDT- 2015/11/17 06:00 PHST- 2015/01/04 [received] PHST- 2015/10/08 [accepted] PHST- 2015/11/13 [aheadofprint] AID - djv323 [pii] AID - 10.1093/jnci/djv323 [doi] PST - epublish SO - J Natl Cancer Inst. 2015 Nov 13;108(2). pii: djv323. doi: 10.1093/jnci/djv323. PMID- 26551625 OWN - NLM STAT- MEDLINE DA - 20151111 DCOM- 20160229 IS - 1423-0232 (Electronic) IS - 0030-2414 (Linking) VI - 89 Suppl 1 DP - 2015 TI - Overview: A New Era of Cancer Genome in Myeloid Malignancies. PG - 1-3 LID - 10.1159/000431054 [doi] AB - In the Myeloid session of the 30th Nagoya International Cancer Treatment Symposium, three speakers were invited. Prof. Clara Bloomfield emphasized the importance of genetic alterations for the prognostic stratification and treatment of acute myeloid leukemia (AML). Dr. Eytan Stein showed that there are promising anti-leukemia effects of IDH2 inhibitor, AG-221, and DOT1L inhibitor, EPZ-5676, based on early-phase clinical studies. Prof. Seishi Ogawa presented a review of the clonal dynamics of secondary myelodysplastic syndrome (MDS) derived from aplastic anemia (AA). From these presentations, we are confident that molecular analysis-based individualized therapies will be realized within a few years. CI - (c) 2015 S. Karger AG, Basel. FAU - Kiyoi, Hitoshi AU - Kiyoi H AD - Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan. LA - eng PT - Journal Article PT - Review DEP - 20151110 PL - Switzerland TA - Oncology JT - Oncology JID - 0135054 RN - 0 (AG-221) RN - 0 (Aminopyridines) RN - 0 (Antineoplastic Agents) RN - 0 (Benzimidazoles) RN - 0 (EPZ-5676) RN - 0 (Immunosuppressive Agents) RN - 0 (Triazines) RN - EC 1.1.1.41 (Isocitrate Dehydrogenase) RN - EC 1.1.1.41 (isocitrate dehydrogenase 2, human) RN - EC 2.1.1.- (DOT1L protein, human) RN - EC 2.1.1.- (Methyltransferases) SB - IM MH - Aminopyridines/pharmacology/therapeutic use MH - Anemia, Aplastic/complications/*genetics MH - Antineoplastic Agents/*pharmacology/therapeutic use MH - Benzimidazoles/pharmacology/therapeutic use MH - *Clonal Evolution/genetics MH - Genome, Human MH - Hematopoiesis/genetics MH - Humans MH - Immunosuppressive Agents/*therapeutic use MH - Isocitrate Dehydrogenase/antagonists & inhibitors MH - Leukemia, Myeloid, Acute/*drug therapy/*genetics MH - Methyltransferases/antagonists & inhibitors MH - *Molecular Targeted Therapy MH - *Mutation MH - Myelodysplastic Syndromes/drug therapy/*genetics MH - Triazines/pharmacology/therapeutic use EDAT- 2015/11/10 06:00 MHDA- 2016/03/02 06:00 CRDT- 2015/11/10 06:00 PHST- 2015/11/10 [aheadofprint] AID - 000431054 [pii] AID - 10.1159/000431054 [doi] PST - ppublish SO - Oncology. 2015;89 Suppl 1:1-3. doi: 10.1159/000431054. Epub 2015 Nov 10. PMID- 26547258 OWN - NLM STAT- MEDLINE DA - 20151125 DCOM- 20160310 LR - 20160101 IS - 1873-5835 (Electronic) IS - 0145-2126 (Linking) VI - 39 IP - 12 DP - 2015 Dec TI - Detectable FLT3-ITD or RAS mutation at the time of transformation from MDS to AML predicts for very poor outcomes. PG - 1367-74 LID - 10.1016/j.leukres.2015.10.005 [doi] LID - S0145-2126(15)30530-0 [pii] AB - BACKGROUND: The molecular events that drive the transformation from myelodysplastic syndromes (MDS) to acute myeloid leukemia (AML) have yet to be fully characterized. We hypothesized that detection of these mutations at the time of transformation from MDS to AML may lead to poorer outcomes. METHODS: We analyzed 102 MDS patients who were admitted to our institution between 2004 and 2013, had wild-type (wt) FLT3-ITD and RAS at diagnosis, progressed to AML, and had serial mutation testing at both the MDS and AML stages. RESULTS: We detected FLT3-ITD and/or RAS mutations in twenty-seven (26%) patients at the time of transformation to AML. Twenty-two patients (81%) had RAS mutations and five (19%) had FLT3-ITD mutations. The median survival after leukemia transformation in patients who had detectable RAS and/or FLT3-ITD mutations was 2.4 months compared to 7.5 months in patients who retained wt RAS and FLT3-ITD (hazard ratio [HR]: 3.08, 95% confidence interval [CI]: 1.9-5.0, p<0.0001). In multivariate analysis, FLT3-ITD and RAS mutations had independent prognostic significance for poor outcome. CI - Copyright (c) 2015 Elsevier Ltd. All rights reserved. FAU - Badar, Talha AU - Badar T AD - Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Patel, Keyur P AU - Patel KP AD - Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Thompson, Philip A AU - Thompson PA AD - Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - DiNardo, Courtney AU - DiNardo C AD - Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Takahashi, Koichi AU - Takahashi K AD - Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Cabrero, Monica AU - Cabrero M AD - Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Borthakur, Gautam AU - Borthakur G AD - Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Cortes, Jorge AU - Cortes J AD - Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Konopleva, Marina AU - Konopleva M AD - Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Kadia, Tapan AU - Kadia T AD - Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Bohannan, Zach AU - Bohannan Z AD - Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Pierce, Sherry AU - Pierce S AD - Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Jabbour, Elias J AU - Jabbour EJ AD - Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Ravandi, Farhad AU - Ravandi F AD - Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Daver, Naval AU - Daver N AD - Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Luthra, Raja AU - Luthra R AD - Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Kantarjian, Hagop AU - Kantarjian H AD - Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Garcia-Manero, Guillermo AU - Garcia-Manero G AD - Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: ggarciam@mdanderson.org. LA - eng GR - P30 CA016672/CA/NCI NIH HHS/United States GR - P30CA016672/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20151019 PL - England TA - Leuk Res JT - Leukemia research JID - 7706787 RN - 0 (Codon) RN - EC 2.7.10.1 (FLT3 protein, human) RN - EC 2.7.10.1 (fms-Like Tyrosine Kinase 3) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Antineoplastic Combined Chemotherapy Protocols/therapeutic use MH - Cell Transformation, Neoplastic/genetics MH - Codon/genetics MH - Disease Progression MH - Female MH - *Genes, ras MH - Humans MH - Kaplan-Meier Estimate MH - Leukemia, Myeloid, Acute/drug therapy/*genetics/pathology MH - Male MH - Middle Aged MH - *Mutation MH - Myelodysplastic Syndromes/*genetics/pathology MH - Prognosis MH - Proportional Hazards Models MH - Retrospective Studies MH - Tandem Repeat Sequences MH - Treatment Outcome MH - fms-Like Tyrosine Kinase 3/*genetics OTO - NOTNLM OT - AML OT - FLT3-ITD OT - Leukemic transformation OT - MDS OT - RAS EDAT- 2015/11/09 06:00 MHDA- 2016/03/11 06:00 CRDT- 2015/11/09 06:00 PHST- 2015/07/22 [received] PHST- 2015/09/21 [revised] PHST- 2015/10/13 [accepted] PHST- 2015/10/19 [aheadofprint] AID - S0145-2126(15)30530-0 [pii] AID - 10.1016/j.leukres.2015.10.005 [doi] PST - ppublish SO - Leuk Res. 2015 Dec;39(12):1367-74. doi: 10.1016/j.leukres.2015.10.005. Epub 2015 Oct 19. PMID- 26545834 OWN - NLM STAT- MEDLINE DA - 20151107 DCOM- 20160311 IS - 1474-5488 (Electronic) IS - 1470-2045 (Linking) VI - 16 IP - 15 DP - 2015 Nov TI - Busulfan-based conditioning regimens: not all partners are equal. PG - 1448-9 LID - 10.1016/S1470-2045(15)00251-X [doi] LID - S1470-2045(15)00251-X [pii] FAU - Giralt, Sergio AU - Giralt S AD - Weill Cornell Medical College, New York, NY, USA; Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: giralts@mskcc.org. LA - eng PT - Comment PT - Journal Article PL - England TA - Lancet Oncol JT - The Lancet. Oncology JID - 100957246 RN - 0 (Antineoplastic Agents) RN - 8N3DW7272P (Cyclophosphamide) RN - FA2DM6879K (Vidarabine) RN - G1LN9045DK (Busulfan) SB - IM CON - Lancet Oncol. 2015 Nov;16(15):1525-36. PMID: 26429297 MH - Antineoplastic Agents/*administration & dosage MH - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use MH - Busulfan/*administration & dosage MH - Cyclophosphamide/*administration & dosage MH - Female MH - *Hematopoietic Stem Cell Transplantation MH - Humans MH - *Induction Chemotherapy MH - Leukemia, Myeloid, Acute/*drug therapy/*surgery MH - Male MH - *Transplantation Conditioning MH - Vidarabine/*analogs & derivatives EDAT- 2015/11/08 06:00 MHDA- 2016/03/12 06:00 CRDT- 2015/11/08 06:00 PHST- 2015/08/17 [received] PHST- 2015/08/17 [accepted] AID - S1470-2045(15)00251-X [pii] AID - 10.1016/S1470-2045(15)00251-X [doi] PST - ppublish SO - Lancet Oncol. 2015 Nov;16(15):1448-9. doi: 10.1016/S1470-2045(15)00251-X. PMID- 26530539 OWN - NLM STAT- MEDLINE DA - 20151125 DCOM- 20160310 IS - 1873-5835 (Electronic) IS - 0145-2126 (Linking) VI - 39 IP - 12 DP - 2015 Dec TI - Outcome of myeloablative allogeneic peripheral blood hematopoietic stem cell transplantation for refractory/relapsed AML patients in NR status. PG - 1375-81 LID - 10.1016/j.leukres.2015.10.011 [doi] LID - S0145-2126(15)30533-6 [pii] AB - To further find effective method to improve the long term survival of refractory or relapsed acute myeloid leukemia (AML) patients, we retrospectively analyzed the outcomes of myeloablative hematopoietic stem cell transplantation (HSCT) for 133 consecutive patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) therapy related AML(t-AML) in not remission status. The overall 3-year OS and DFS were 40.9% and 35.6% respectively. The variables associated with improved long term DFS were a bone marrow blast cell count less than 20% and an intensified conditioning regimen. In addition, the t-AML group had higher rates of relapse and III-IV acute GVHD than the primary AML group. The unrelated donor group had similar OS and DFS with sibling groups. Our study suggested that decreasing bone marrow blast cell counts before HSCT and strengthening the conditioning regimen may improve long-term DFS for refractory/relapsed AML patients, and unrelated donor group can get similar effect when compared to the sibling group. CI - Copyright (c) 2015 Elsevier Ltd. All rights reserved. FAU - Liu, Na AU - Liu N AD - Department of Hematopoietic Stem Cell Transplantation Center, Affiliated Hospital to Academy of Military Medical Science (307Hospital, PLA), China. FAU - Ning, Hong-Mei AU - Ning HM AD - Department of Hematopoietic Stem Cell Transplantation Center, Affiliated Hospital to Academy of Military Medical Science (307Hospital, PLA), China. FAU - Hu, Liang-Ding AU - Hu LD AD - Department of Hematopoietic Stem Cell Transplantation Center, Affiliated Hospital to Academy of Military Medical Science (307Hospital, PLA), China. FAU - Jiang, Min AU - Jiang M AD - Department of Hematopoietic Stem Cell Transplantation Center, Affiliated Hospital to Academy of Military Medical Science (307Hospital, PLA), China. FAU - Xu, Chen AU - Xu C AD - Department of Hematopoietic Stem Cell Transplantation Center, Affiliated Hospital to Academy of Military Medical Science (307Hospital, PLA), China. FAU - Hu, Jiang-Wei AU - Hu JW AD - Department of Hematopoietic Stem Cell Transplantation Center, Affiliated Hospital to Academy of Military Medical Science (307Hospital, PLA), China. FAU - Wang, Jun AU - Wang J AD - Department of Hematopoietic Stem Cell Transplantation Center, Affiliated Hospital to Academy of Military Medical Science (307Hospital, PLA), China. FAU - Li, Yu-Hang AU - Li YH AD - Department of Hematopoietic Stem Cell Transplantation Center, Affiliated Hospital to Academy of Military Medical Science (307Hospital, PLA), China. FAU - Li, Bo-Tao AU - Li BT AD - Department of Hematopoietic Stem Cell Transplantation Center, Affiliated Hospital to Academy of Military Medical Science (307Hospital, PLA), China. FAU - Lou, Xiao AU - Lou X AD - Department of Hematopoietic Stem Cell Transplantation Center, Affiliated Hospital to Academy of Military Medical Science (307Hospital, PLA), China. FAU - Yang, Fan AU - Yang F AD - Department of Hematopoietic Stem Cell Transplantation Center, Affiliated Hospital to Academy of Military Medical Science (307Hospital, PLA), China. FAU - Chen, Jian-Lin AU - Chen JL AD - Department of Hematopoietic Stem Cell Transplantation Center, Affiliated Hospital to Academy of Military Medical Science (307Hospital, PLA), China. FAU - Su, Yong-Feng AU - Su YF AD - Department of Hematopoietic Stem Cell Transplantation Center, Affiliated Hospital to Academy of Military Medical Science (307Hospital, PLA), China. FAU - Li, Meng AU - Li M AD - Department of Hematopoietic Stem Cell Transplantation Center, Affiliated Hospital to Academy of Military Medical Science (307Hospital, PLA), China. FAU - Wang, Hong-Ye AU - Wang HY AD - Department of Hematopoietic Stem Cell Transplantation Center, Affiliated Hospital to Academy of Military Medical Science (307Hospital, PLA), China. FAU - Ren, Jing AU - Ren J AD - Department of Hematopoietic Stem Cell Transplantation Center, Affiliated Hospital to Academy of Military Medical Science (307Hospital, PLA), China. FAU - Feng, Yue-Qian AU - Feng YQ AD - Department of Hematopoietic Stem Cell Transplantation Center, Affiliated Hospital to Academy of Military Medical Science (307Hospital, PLA), China. FAU - Zhang, Bin AU - Zhang B AD - Department of Hematopoietic Stem Cell Transplantation Center, Affiliated Hospital to Academy of Military Medical Science (307Hospital, PLA), China. FAU - Wang, Dan-Hong AU - Wang DH AD - Department of Hematopoietic Stem Cell Transplantation Center, Affiliated Hospital to Academy of Military Medical Science (307Hospital, PLA), China. FAU - Chen, Hu AU - Chen H AD - Department of Hematopoietic Stem Cell Transplantation Center, Affiliated Hospital to Academy of Military Medical Science (307Hospital, PLA), China. Electronic address: chenhu217@aliyun.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151019 PL - England TA - Leuk Res JT - Leukemia research JID - 7706787 RN - 0 (Immunosuppressive Agents) RN - 0 (Myeloablative Agonists) SB - IM MH - Adolescent MH - Adult MH - Allografts MH - Antineoplastic Combined Chemotherapy Protocols/therapeutic use MH - Combined Modality Therapy MH - Disease-Free Survival MH - Female MH - Graft vs Host Disease/prevention & control MH - Histocompatibility MH - Humans MH - Immunosuppressive Agents/therapeutic use MH - Kaplan-Meier Estimate MH - Leukemia, Myeloid, Acute/drug therapy/*therapy MH - Living Donors MH - Lymphocyte Count MH - Male MH - Middle Aged MH - Myeloablative Agonists/*therapeutic use MH - Neoplastic Stem Cells MH - *Peripheral Blood Stem Cell Transplantation MH - Recurrence MH - Retrospective Studies MH - Siblings MH - Transplantation Conditioning/*methods/mortality MH - Treatment Outcome OTO - NOTNLM OT - Acute myeloid leukemia OT - Blast cells OT - Hematopoietic stem cell transplantation OT - Intensified conditioning regimen OT - Myelodysplastic syndrome OT - Refractory EDAT- 2015/11/05 06:00 MHDA- 2016/03/11 06:00 CRDT- 2015/11/05 06:00 PHST- 2015/07/02 [received] PHST- 2015/10/13 [revised] PHST- 2015/10/14 [accepted] PHST- 2015/10/19 [aheadofprint] AID - S0145-2126(15)30533-6 [pii] AID - 10.1016/j.leukres.2015.10.011 [doi] PST - ppublish SO - Leuk Res. 2015 Dec;39(12):1375-81. doi: 10.1016/j.leukres.2015.10.011. Epub 2015 Oct 19. PMID- 26521988 OWN - NLM STAT- MEDLINE DA - 20151125 DCOM- 20160310 IS - 1873-5835 (Electronic) IS - 0145-2126 (Linking) VI - 39 IP - 12 DP - 2015 Dec TI - Clinical activity of alvocidib (flavopiridol) in acute myeloid leukemia. PG - 1312-8 LID - 10.1016/j.leukres.2015.10.010 [doi] LID - S0145-2126(15)30536-1 [pii] AB - There have been minimal therapeutic advancements in acute myeloid leukemia (AML) over the past 4 decades and outcomes remain unsatisfactory. Alvocidib (formerly flavopiridol) is a multi-serine threonine cyclin-dependent kinase inhibitor with demonstrable in vitro and clinical activity in AML when combined in a timed sequential chemotherapy regimen, FLAM (alvocidib followed by cytarabine continuous infusion and mitoxantrone). FLAM has been evaluated in sequential phase 1 and phase 2 studies in 149 and 256 relapsed/refractory and newly diagnosed non-favorable risk AML patients, respectively, with encouraging findings in both patient populations warranting further investigation. This review highlights the mechanism of action of alvocidib, pre-clinical studies of alvocidib in AML, and the clinical trials evaluating alvocidib alone and in combination with cytotoxic agents (FLAM) in AML. CI - Copyright (c) 2015 Elsevier Ltd. All rights reserved. FAU - Zeidner, Joshua F AU - Zeidner JF AD - University of North Carolina, Lineberger Comprehensive Cancer Center, Chapel Hill, NC, United States. Electronic address: Joshua_Zeidner@med.unc.edu. FAU - Karp, Judith E AU - Karp JE AD - Johns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, United States. LA - eng PT - Journal Article PT - Review DEP - 20151019 PL - England TA - Leuk Res JT - Leukemia research JID - 7706787 RN - 0 (Antineoplastic Agents) RN - 0 (Biomarkers, Tumor) RN - 0 (Flavonoids) RN - 0 (MCL1 protein, human) RN - 0 (Myeloid Cell Leukemia Sequence 1 Protein) RN - 0 (Neoplasm Proteins) RN - 0 (Piperidines) RN - 0 (Protein Kinase Inhibitors) RN - 45AD6X575G (alvocidib) RN - EC 2.7.11.22 (Cyclin-Dependent Kinases) SB - IM MH - Antineoplastic Agents/adverse effects/*therapeutic use MH - Antineoplastic Combined Chemotherapy Protocols/therapeutic use MH - Biomarkers, Tumor MH - Cell Cycle/drug effects MH - Cyclin-Dependent Kinases/*antagonists & inhibitors MH - Drug Interactions MH - Drug Screening Assays, Antitumor MH - Flavonoids/administration & dosage/adverse effects/pharmacology/*therapeutic use MH - Humans MH - Leukemia, Myeloid, Acute/*drug therapy/enzymology MH - Molecular Structure MH - *Molecular Targeted Therapy MH - Myeloid Cell Leukemia Sequence 1 Protein/analysis/biosynthesis MH - Neoplasm Proteins/*antagonists & inhibitors MH - Piperidines/administration & dosage/adverse effects/pharmacology/*therapeutic use MH - Protein Kinase Inhibitors/adverse effects/*therapeutic use MH - Salvage Therapy MH - Tumor Lysis Syndrome/etiology OTO - NOTNLM OT - Acute myeloid leukemia OT - Alvocidib OT - CDK inhibitors OT - Cyclin dependent kinase OT - FLAM OT - Flavopiridol EDAT- 2015/11/03 06:00 MHDA- 2016/03/11 06:00 CRDT- 2015/11/03 06:00 PHST- 2015/09/02 [received] PHST- 2015/10/01 [revised] PHST- 2015/10/14 [accepted] PHST- 2015/10/19 [aheadofprint] AID - S0145-2126(15)30536-1 [pii] AID - 10.1016/j.leukres.2015.10.010 [doi] PST - ppublish SO - Leuk Res. 2015 Dec;39(12):1312-8. doi: 10.1016/j.leukres.2015.10.010. Epub 2015 Oct 19. PMID- 26492932 OWN - NLM STAT- MEDLINE DA - 20151127 DCOM- 20160318 LR - 20160326 IS - 1528-0020 (Electronic) IS - 0006-4971 (Linking) VI - 126 IP - 22 DP - 2015 Nov 26 TI - Genomic analysis of germ line and somatic variants in familial myelodysplasia/acute myeloid leukemia. PG - 2484-90 LID - 10.1182/blood-2015-04-641100 [doi] AB - Familial clustering of myelodysplastic syndromes (MDSs) and acute myeloid leukemia (AML) can be caused by inherited factors. We screened 59 individuals from 17 families with 2 or more biological relatives with MDS/AML for variants in 12 genes with established roles in predisposition to MDS/AML, and identified a pathogenic germ line variant in 5 families (29%). Extending the screen with a panel of 264 genes that are recurrently mutated in de novo AML, we identified rare, nonsynonymous germ line variants in 4 genes, each segregating with MDS/AML in 2 families. Somatic mutations are required for progression to MDS/AML in these familial cases. Using a combination of targeted and exome sequencing of tumor and matched normal samples from 26 familial MDS/AML cases and asymptomatic carriers, we identified recurrent frameshift mutations in the cohesin-associated factor PDS5B, co-occurrence of somatic ASXL1 mutations with germ line GATA2 mutations, and recurrent mutations in other known MDS/AML drivers. Mutations in genes that are recurrently mutated in de novo AML were underrepresented in the familial MDS/AML cases, although the total number of somatic mutations per exome was the same. Lastly, clonal skewing of hematopoiesis was detected in 67% of young, asymptomatic RUNX1 carriers, providing a potential biomarker that could be used for surveillance in these high-risk families. CI - (c) 2015 by The American Society of Hematology. FAU - Churpek, Jane E AU - Churpek JE AD - Section of Hematology/Oncology, Center for Clinical Cancer Genetics, The University of Chicago, Chicago, IL; FAU - Pyrtel, Khateriaa AU - Pyrtel K AD - Siteman Cancer Center. FAU - Kanchi, Krishna-Latha AU - Kanchi KL AD - The Genome Institute, and. FAU - Shao, Jin AU - Shao J AD - Siteman Cancer Center. FAU - Koboldt, Daniel AU - Koboldt D AD - Siteman Cancer Center, The Genome Institute, and Division of Oncology, Department of Medicine, Washington University, St Louis, MO; FAU - Miller, Christopher A AU - Miller CA AD - The Genome Institute, and. FAU - Shen, Dong AU - Shen D AD - Medimmune/AstraZeneca, Gaithersburg, MD; FAU - Fulton, Robert AU - Fulton R AD - The Genome Institute, and. FAU - O'Laughlin, Michelle AU - O'Laughlin M AD - The Genome Institute, and. FAU - Fronick, Catrina AU - Fronick C AD - The Genome Institute, and. FAU - Pusic, Iskra AU - Pusic I AD - Division of Oncology, Department of Medicine, Washington University, St Louis, MO; FAU - Uy, Geoffrey L AU - Uy GL AD - Division of Oncology, Department of Medicine, Washington University, St Louis, MO; FAU - Braunstein, Evan M AU - Braunstein EM AD - Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD; FAU - Levis, Mark AU - Levis M AD - Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD; FAU - Ross, Julie AU - Ross J AD - Department of Medicine, University of Minnesota, Minneapolis, MN; and. FAU - Elliott, Kevin AU - Elliott K AD - Siteman Cancer Center. FAU - Heath, Sharon AU - Heath S AD - Siteman Cancer Center. FAU - Jiang, Allan AU - Jiang A AD - Division of Oncology, Department of Medicine, Washington University, St Louis, MO; FAU - Westervelt, Peter AU - Westervelt P AD - Siteman Cancer Center, Division of Oncology, Department of Medicine, Washington University, St Louis, MO; FAU - DiPersio, John F AU - DiPersio JF AD - Siteman Cancer Center, Division of Oncology, Department of Medicine, Washington University, St Louis, MO; FAU - Link, Daniel C AU - Link DC AD - Siteman Cancer Center, Division of Oncology, Department of Medicine, Washington University, St Louis, MO; FAU - Walter, Matthew J AU - Walter MJ AD - Siteman Cancer Center, Division of Oncology, Department of Medicine, Washington University, St Louis, MO; FAU - Welch, John AU - Welch J AD - Siteman Cancer Center, Division of Oncology, Department of Medicine, Washington University, St Louis, MO; FAU - Wilson, Richard AU - Wilson R AD - Siteman Cancer Center, The Genome Institute, and. FAU - Ley, Timothy J AU - Ley TJ AD - Siteman Cancer Center, The Genome Institute, and Division of Oncology, Department of Medicine, Washington University, St Louis, MO; FAU - Godley, Lucy A AU - Godley LA AD - Section of Hematology/Oncology, Center for Clinical Cancer Genetics, The University of Chicago, Chicago, IL; FAU - Graubert, Timothy A AU - Graubert TA AD - Massachusetts General Hospital Cancer Center, Boston, MA. LA - eng SI - PIR/116897 SI - PIR/601399 GR - CA101937/CA/NCI NIH HHS/United States GR - CA157439/CA/NCI NIH HHS/United States GR - K12 CA139160/CA/NCI NIH HHS/United States GR - K12 HL087169/HL/NHLBI NIH HHS/United States GR - P01 CA101937/CA/NCI NIH HHS/United States GR - T32 HL007525/HL/NHLBI NIH HHS/United States GR - UL1 TR000430/TR/NCATS NIH HHS/United States PT - Clinical Trial PT - Journal Article PT - Multicenter Study PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20151022 PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (ASXL1 protein, human) RN - 0 (Core Binding Factor Alpha 2 Subunit) RN - 0 (DNA-Binding Proteins) RN - 0 (Neoplasm Proteins) RN - 0 (PDS5B protein, human) RN - 0 (RUNX1 protein, human) RN - 0 (Repressor Proteins) RN - 0 (Transcription Factors) SB - AIM SB - IM MH - Adolescent MH - Adult MH - Aged MH - Base Sequence MH - Child MH - Core Binding Factor Alpha 2 Subunit MH - DNA-Binding Proteins/genetics MH - *Exome MH - Female MH - Genetic Diseases, Inborn/*genetics MH - *Germ-Line Mutation MH - Hematopoiesis/genetics MH - Humans MH - Leukemia, Myeloid, Acute/*genetics MH - Male MH - Middle Aged MH - Molecular Sequence Data MH - Myelodysplastic Syndromes/*genetics MH - Neoplasm Proteins/*genetics MH - Repressor Proteins/genetics MH - Transcription Factors/genetics PMC - PMC4661171 OID - NLM: PMC4661171 [Available on 11/26/16] EDAT- 2015/10/24 06:00 MHDA- 2016/03/19 06:00 CRDT- 2015/10/24 06:00 PMCR- 2016/11/26 00:00 PHST- 2015/04/16 [received] PHST- 2015/08/31 [accepted] PHST- 2015/10/22 [aheadofprint] AID - blood-2015-04-641100 [pii] AID - 10.1182/blood-2015-04-641100 [doi] PST - ppublish SO - Blood. 2015 Nov 26;126(22):2484-90. doi: 10.1182/blood-2015-04-641100. Epub 2015 Oct 22. PMID- 26453660 OWN - NLM STAT- MEDLINE DA - 20151127 DCOM- 20160318 IS - 1528-0020 (Electronic) IS - 0006-4971 (Linking) VI - 126 IP - 22 DP - 2015 Nov 26 TI - Time to improve health-related quality of life outcomes in patients with acute promyelocytic leukemia. PG - 2523-4 LID - 10.1182/blood-2015-07-658922 [doi] FAU - Efficace, Fabio AU - Efficace F AD - Italian Group for Adult Hematologic Diseases (GIMEMA), Data Center and Health Outcomes Research Unit, Rome, Italy. FAU - Mandelli, Franco AU - Mandelli F AD - Italian Group for Adult Hematologic Diseases (GIMEMA), Data Center and Health Outcomes Research Unit, Rome, Italy. FAU - Platzbecker, Uwe AU - Platzbecker U AD - Department of Medicine I, University Hospital Dresden "Carl Gustav Carus," Dresden, Germany. FAU - Cottone, Francesco AU - Cottone F AD - Italian Group for Adult Hematologic Diseases (GIMEMA), Data Center and Health Outcomes Research Unit, Rome, Italy. FAU - Lo Coco, Francesco AU - Lo Coco F AD - Dipartimento di Biomedicina e Prevenzione, Universita Tor Vergata, Roma, Italy. LA - eng PT - Letter DEP - 20151009 PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Arsenicals) RN - 0 (Oxides) RN - 5688UTC01R (Tretinoin) RN - S7V92P67HO (arsenic trioxide) SB - AIM SB - IM MH - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage MH - Arsenicals/administration & dosage MH - Disease-Free Survival MH - Female MH - Humans MH - Leukemia, Promyelocytic, Acute/*drug therapy/*mortality MH - Male MH - Middle Aged MH - Oxides/administration & dosage MH - *Quality of Life MH - Survival Rate MH - Tretinoin/administration & dosage EDAT- 2015/10/11 06:00 MHDA- 2016/03/19 06:00 CRDT- 2015/10/11 06:00 PHST- 2015/10/09 [aheadofprint] AID - blood-2015-07-658922 [pii] AID - 10.1182/blood-2015-07-658922 [doi] PST - ppublish SO - Blood. 2015 Nov 26;126(22):2523-4. doi: 10.1182/blood-2015-07-658922. Epub 2015 Oct 9. PMID- 26445329 OWN - NLM STAT- MEDLINE DA - 20151008 DCOM- 20160325 LR - 20151125 IS - 1414-431X (Electronic) IS - 0100-879X (Linking) VI - 48 IP - 10 DP - 2015 Oct TI - Salvaged single-unit cord blood transplantation for 26 patients with hematologic malignancies not in remission. PG - 871-6 LID - 10.1590/1414-431X20154389 [doi] LID - S0100-879X2015001000002 [pii] AB - Treatments for patients with hematologic malignancies not in remission are limited, but a few clinical studies have investigated the effects of salvaged unrelated cord blood transplantation (CBT). We retrospectively studied 19 patients with acute leukemia, 5 with myelodysplastic syndrome (MDS with refractory anemia with excess blasts [RAEB]), and 2 with non-Hodgkin's lymphoma who received 1 CBT unit 20 x 10(9)/L on median day +35 (range 17-70 days). Sixteen patients (61.5%) experienced pre-engraftment syndrome (PES), and six (23.1%) patients progressed to acute graft-versus-host disease (GVHD). The cumulative incidence rates of II-IV acute GVHD and chronic GVHD were 50% and 26.9%, respectively. After a median follow-up of 27 months (range 5-74), 14 patients survived and 3 relapsed. The estimated 2-year overall survival (OS), disease-free survival (DFS), and non-relapse mortality (NRM) rates were 50.5%, 40.3%, and 35.2%, respectively. Salvaged CBT might be a promising modality for treating hematologic malignancies, even in patients with a high leukemia burden. FAU - Yao, W AU - Yao W AD - School of Medicine, Shandong University, Jinan, CN. FAU - Zheng, C C AU - Zheng CC AD - Department of Hematology, Anhui Provincial Hospital, Anhui Medical University, Hefei, CN. FAU - Liu, H L AU - Liu HL AD - Department of Hematology, Anhui Provincial Hospital, Anhui Medical University, Hefei, CN. FAU - Geng, L Q AU - Geng LQ AD - Department of Hematology, Anhui Provincial Hospital, Anhui Medical University, Hefei, CN. FAU - Tang, B L AU - Tang BL AD - Department of Hematology, Anhui Provincial Hospital, Anhui Medical University, Hefei, CN. FAU - Tong, J AU - Tong J AD - Department of Hematology, Anhui Provincial Hospital, Anhui Medical University, Hefei, CN. FAU - Zhu, X Y AU - Zhu XY AD - Department of Hematology, Anhui Provincial Hospital, Anhui Medical University, Hefei, CN. FAU - Song, K D AU - Song KD AD - Department of Hematology, Anhui Provincial Hospital, Anhui Medical University, Hefei, CN. FAU - Qiang, P AU - Qiang P AD - Department of Hematology, Anhui Provincial Hospital, Anhui Medical University, Hefei, CN. FAU - Sun, Z M AU - Sun ZM AD - School of Medicine, Shandong University, Jinan, CN. LA - eng PT - Clinical Study PT - Journal Article DEP - 20150327 PL - Brazil TA - Braz J Med Biol Res JT - Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas / Sociedade Brasileira de Biofisica ... [et al.] JID - 8112917 SB - IM MH - Adolescent MH - Adult MH - *Allografts MH - Anemia, Refractory, with Excess of Blasts/mortality/*therapy MH - Child MH - *Cord Blood Stem Cell Transplantation/mortality MH - Disease-Free Survival MH - Female MH - Follow-Up Studies MH - *Graft vs Host Disease/mortality MH - Hematologic Neoplasms/mortality/therapy MH - Humans MH - Leukemia/mortality/therapy MH - Leukemia, Biphenotypic, Acute/mortality/*therapy MH - Leukemia, Lymphoid/mortality/therapy MH - Leukemia, Myeloid/mortality/therapy MH - Lymphoma, Non-Hodgkin/mortality/*therapy MH - Male MH - Myelodysplastic Syndromes/mortality/therapy MH - Remission Induction/methods MH - Retrospective Studies MH - Treatment Outcome MH - Young Adult PMC - PMC4617112 OID - NLM: PMC4617112 EDAT- 2015/10/09 06:00 MHDA- 2016/03/26 06:00 CRDT- 2015/10/08 06:00 PHST- 2014/09/29 [received] PHST- 2015/01/13 [accepted] PHST- 2015/03/27 [aheadofprint] AID - S0100-879X2015001000002 [pii] AID - 10.1590/1414-431X20154389 [doi] PST - ppublish SO - Braz J Med Biol Res. 2015 Oct;48(10):871-6. doi: 10.1590/1414-431X20154389. Epub 2015 Mar 27. PMID- 26438511 OWN - NLM STAT- MEDLINE DA - 20151127 DCOM- 20160318 LR - 20151209 IS - 1528-0020 (Electronic) IS - 0006-4971 (Linking) VI - 126 IP - 22 DP - 2015 Nov 26 TI - Profiling of somatic mutations in acute myeloid leukemia with FLT3-ITD at diagnosis and relapse. PG - 2491-501 LID - 10.1182/blood-2015-05-646240 [doi] AB - Acute myeloid leukemia (AML) with an FLT3 internal tandem duplication (FLT3-ITD) mutation is an aggressive hematologic malignancy with a grave prognosis. To identify the mutational spectrum associated with relapse, whole-exome sequencing was performed on 13 matched diagnosis, relapse, and remission trios followed by targeted sequencing of 299 genes in 67 FLT3-ITD patients. The FLT3-ITD genome has an average of 13 mutations per sample, similar to other AML subtypes, which is a low mutation rate compared with that in solid tumors. Recurrent mutations occur in genes related to DNA methylation, chromatin, histone methylation, myeloid transcription factors, signaling, adhesion, cohesin complex, and the spliceosome. Their pattern of mutual exclusivity and cooperation among mutated genes suggests that these genes have a strong biological relationship. In addition, we identified mutations in previously unappreciated genes such as MLL3, NSD1, FAT1, FAT4, and IDH3B. Mutations in 9 genes were observed in the relapse-specific phase. DNMT3A mutations are the most stable mutations, and this DNMT3A-transformed clone can be present even in morphologic complete remissions. Of note, all AML matched trio samples shared at least 1 genomic alteration at diagnosis and relapse, suggesting common ancestral clones. Two types of clonal evolution occur at relapse: either the founder clone recurs or a subclone of the founder clone escapes from induction chemotherapy and expands at relapse by acquiring new mutations. Relapse-specific mutations displayed an increase in transversions. Functional assays demonstrated that both MLL3 and FAT1 exert tumor-suppressor activity in the FLT3-ITD subtype. An inhibitor of XPO1 synergized with standard AML induction chemotherapy to inhibit FLT3-ITD growth. This study clearly shows that FLT3-ITD AML requires additional driver genetic alterations in addition to FLT3-ITD alone. CI - (c) 2015 by The American Society of Hematology. FAU - Garg, Manoj AU - Garg M AUID- ORCID: http://orcid.org/0000-0002-3492-2957 AD - Cancer Science Institute of Singapore, National University of Singapore, Singapore; FAU - Nagata, Yasunobu AU - Nagata Y AD - Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan; FAU - Kanojia, Deepika AU - Kanojia D AD - Cancer Science Institute of Singapore, National University of Singapore, Singapore; FAU - Mayakonda, Anand AU - Mayakonda A AD - Cancer Science Institute of Singapore, National University of Singapore, Singapore; FAU - Yoshida, Kenichi AU - Yoshida K AD - Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan; FAU - Haridas Keloth, Sreya AU - Haridas Keloth S AD - Cancer Science Institute of Singapore, National University of Singapore, Singapore; FAU - Zang, Zhi Jiang AU - Zang ZJ AD - Cancer Science Institute of Singapore, National University of Singapore, Singapore; FAU - Okuno, Yusuke AU - Okuno Y AD - Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan; FAU - Shiraishi, Yuichi AU - Shiraishi Y AD - Laboratory of DNA Information Analysis, and. FAU - Chiba, Kenichi AU - Chiba K AD - Laboratory of DNA Information Analysis, and. FAU - Tanaka, Hiroko AU - Tanaka H AD - Laboratory of Sequence Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan; FAU - Miyano, Satoru AU - Miyano S AD - Laboratory of Sequence Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan; FAU - Ding, Ling-Wen AU - Ding LW AD - Cancer Science Institute of Singapore, National University of Singapore, Singapore; FAU - Alpermann, Tamara AU - Alpermann T AD - Munich Leukemia Laboratory, Munich, Germany; FAU - Sun, Qiao-Yang AU - Sun QY AD - Cancer Science Institute of Singapore, National University of Singapore, Singapore; FAU - Lin, De-Chen AU - Lin DC AD - Cancer Science Institute of Singapore, National University of Singapore, Singapore; FAU - Chien, Wenwen AU - Chien W AD - Cancer Science Institute of Singapore, National University of Singapore, Singapore; FAU - Madan, Vikas AU - Madan V AD - Cancer Science Institute of Singapore, National University of Singapore, Singapore; FAU - Liu, Li-Zhen AU - Liu LZ AD - Cancer Science Institute of Singapore, National University of Singapore, Singapore; FAU - Tan, Kar-Tong AU - Tan KT AD - Cancer Science Institute of Singapore, National University of Singapore, Singapore; FAU - Sampath, Abhishek AU - Sampath A AD - Cancer Science Institute of Singapore, National University of Singapore, Singapore; FAU - Venkatesan, Subhashree AU - Venkatesan S AD - Cancer Science Institute of Singapore, National University of Singapore, Singapore; FAU - Inokuchi, Koiti AU - Inokuchi K AD - Department of Hematology, Nippon Medical School, Tokyo, Japan; FAU - Wakita, Satoshi AU - Wakita S AD - Department of Hematology, Nippon Medical School, Tokyo, Japan; FAU - Yamaguchi, Hiroki AU - Yamaguchi H AD - Department of Hematology, Nippon Medical School, Tokyo, Japan; FAU - Chng, Wee Joo AU - Chng WJ AD - Cancer Science Institute of Singapore, National University of Singapore, Singapore; FAU - Kham, Shirley-Kow Yin AU - Kham SK AD - Department of Paediatrics, National University Health System, Singapore; FAU - Yeoh, Allen Eng-Juh AU - Yeoh AE AD - Department of Paediatrics, National University Health System, Singapore; FAU - Sanada, Masashi AU - Sanada M AD - Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Department of Advanced Diagnosis, Clinical Research Center, Nagoya Medical Center, Nagoya, Japan; FAU - Schiller, Joanna AU - Schiller J AD - Department I of Internal Medicine, University of Cologne, Cologne, Germany; FAU - Kreuzer, Karl-Anton AU - Kreuzer KA AD - Department I of Internal Medicine, University of Cologne, Cologne, Germany; FAU - Kornblau, Steven M AU - Kornblau SM AD - Department of Leukemia, MD Anderson Cancer Center, Houston, TX; Section of Molecular Hematology and Therapy, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX; FAU - Kantarjian, Hagop M AU - Kantarjian HM AD - Department of Leukemia, MD Anderson Cancer Center, Houston, TX; Section of Molecular Hematology and Therapy, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX; FAU - Haferlach, Torsten AU - Haferlach T AD - Munich Leukemia Laboratory, Munich, Germany; FAU - Lill, Michael AU - Lill M AD - Cedars-Sinai Medical Center, Division of Hematology/Oncology, University of California Los Angeles, School of Medicine, Los Angeles, CA; FAU - Kuo, Ming-Chung AU - Kuo MC AD - Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taipei, Taiwan; FAU - Shih, Lee-Yung AU - Shih LY AD - Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taipei, Taiwan; FAU - Blau, Igor-Wolfgang AU - Blau IW AD - Department of Hematology, Oncology and Tumorimmunology, Charite University School of Medicine, Berlin, Germany; and. FAU - Blau, Olga AU - Blau O AD - Department of Hematology, Oncology and Tumorimmunology, Charite University School of Medicine, Berlin, Germany; and. FAU - Yang, Henry AU - Yang H AD - Cancer Science Institute of Singapore, National University of Singapore, Singapore; FAU - Ogawa, Seishi AU - Ogawa S AD - Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan; FAU - Koeffler, H Phillip AU - Koeffler HP AD - Cancer Science Institute of Singapore, National University of Singapore, Singapore; Cedars-Sinai Medical Center, Division of Hematology/Oncology, University of California Los Angeles, School of Medicine, Los Angeles, CA; National University Cancer Institute, National University Hospital, Singapore. LA - eng GR - R01CA026038-35/CA/NCI NIH HHS/United States PT - Journal Article PT - Multicenter Study PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20151005 PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Chromatin) RN - EC 2.7.10.1 (FLT3 protein, human) RN - EC 2.7.10.1 (fms-Like Tyrosine Kinase 3) SB - AIM SB - IM MH - Chromatin/genetics/metabolism MH - DNA Methylation/genetics MH - *Exome MH - Female MH - Humans MH - Induction Chemotherapy MH - *Leukemia, Myeloid, Acute/drug therapy/genetics/mortality MH - Male MH - *Mutation MH - Recurrence MH - Retrospective Studies MH - fms-Like Tyrosine Kinase 3/*genetics PMC - PMC4661172 OID - NLM: PMC4661172 [Available on 11/26/16] EDAT- 2015/10/07 06:00 MHDA- 2016/03/19 06:00 CRDT- 2015/10/07 06:00 PMCR- 2016/11/26 00:00 PHST- 2015/05/18 [received] PHST- 2015/09/22 [accepted] PHST- 2015/10/05 [aheadofprint] AID - blood-2015-05-646240 [pii] AID - 10.1182/blood-2015-05-646240 [doi] PST - ppublish SO - Blood. 2015 Nov 26;126(22):2491-501. doi: 10.1182/blood-2015-05-646240. Epub 2015 Oct 5. PMID- 26432074 OWN - NLM STAT- MEDLINE DA - 20151125 DCOM- 20160310 IS - 1873-5835 (Electronic) IS - 0145-2126 (Linking) VI - 39 IP - 12 DP - 2015 Dec TI - Increasing aclarubicin dosage of the conventional CAG (low-dose cytarabine and aclarubicin in combination with granulocyte colony-stimulating factor) regimen is more efficacious as a salvage therapy than CAG for relapsed/refractory acute myeloid leukemia. PG - 1353-9 LID - 10.1016/j.leukres.2015.09.014 [doi] LID - S0145-2126(15)30385-4 [pii] AB - The efficacy and safety of a modified CAG (low-dose cytarabine and aclarubicin in combination with granulocyte colony-stimulating factor) regimen with an increased aclarubicin dosage [high-dose (HD)-CAG] were observed in 145 patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) and compared to the results of 172 patients treated with a conventional CAG regimen. The HD-CAG regimen showed both a higher complete remission (CR) rate (60.7% vs. 46.5%, P=0.013) and overall response (OR) rate (74.5% vs. 63.4%, P=0.039) than CAG. For patients aged <60 years, HD-CAG manifested an efficacy advantage over the CAG regimen (62.6% vs. 47.4%, P=0.015). The 4-year overall survival (OS) rate was 30.3%+/-13.2% with a median survival time of 19.0+/-5.4 months for patients re-induced with the HD-CAG regimen, which showed no significant difference compared to the CAG regimen (with a 4-year OS rate of 18.2%+/-5.3% and a median survival time of 16.0+/-3.6 months, P=0.485). The main adverse effect was myelosuppression; platelet recovery over 50x10(9)/L was extended by the HD-CAG regimen (15 days vs. 10 days of the CAG regimen, P=0.003), which was tolerable and manageable. HD-CAG can safely improve efficacy compared to the CAG regimen and thus serves as an alternative treatment for R/R AML. CI - Copyright (c) 2015 Elsevier Ltd. All rights reserved. FAU - Qu, Qi AU - Qu Q AD - The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Key laboratory of Thrombosis and Hemostasis of Ministry of Health, Collaborative Innovation Center of Hematology, National Clinical Key Subject Construction Project, Suzhou 215006, PR China. FAU - Liu, Limin AU - Liu L AD - The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Key laboratory of Thrombosis and Hemostasis of Ministry of Health, Collaborative Innovation Center of Hematology, National Clinical Key Subject Construction Project, Suzhou 215006, PR China. FAU - Zhang, Yanming AU - Zhang Y AD - Department of Hematology, Huai'an Hospital Affiliated to Xuzhou Medical College, The Second People's Hospital of Huai'an City, Huai'an, Jiangsu Province 223002, PR China. FAU - Li, Xiaoli AU - Li X AD - The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Key laboratory of Thrombosis and Hemostasis of Ministry of Health, Collaborative Innovation Center of Hematology, National Clinical Key Subject Construction Project, Suzhou 215006, PR China. FAU - Wu, Depei AU - Wu D AD - The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Key laboratory of Thrombosis and Hemostasis of Ministry of Health, Collaborative Innovation Center of Hematology, National Clinical Key Subject Construction Project, Suzhou 215006, PR China. Electronic address: wudepei@medmail.com.cn. LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150918 PL - England TA - Leuk Res JT - Leukemia research JID - 7706787 RN - 04079A1RDZ (Cytarabine) RN - 143011-72-7 (Granulocyte Colony-Stimulating Factor) RN - 74KXF8I502 (Aclarubicin) SB - IM MH - Aclarubicin/administration & dosage/adverse effects MH - Adolescent MH - Adult MH - Aged MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use MH - Bone Marrow Diseases/chemically induced MH - Cardiomyopathies/chemically induced MH - Cytarabine/administration & dosage/adverse effects MH - Dose-Response Relationship, Drug MH - Drug-Induced Liver Injury/etiology MH - Female MH - Granulocyte Colony-Stimulating Factor/administration & dosage MH - Humans MH - Kaplan-Meier Estimate MH - Kidney Diseases/chemically induced MH - Leukemia, Myeloid, Acute/*drug therapy MH - Male MH - Middle Aged MH - Proportional Hazards Models MH - Recurrence MH - Remission Induction MH - Retrospective Studies MH - *Salvage Therapy MH - Treatment Outcome MH - Young Adult OTO - NOTNLM OT - Acute myeloid leukemia OT - CAG protocol OT - Refractory OT - Relapse OT - Salvage therapy EDAT- 2015/10/04 06:00 MHDA- 2016/03/11 06:00 CRDT- 2015/10/04 06:00 PHST- 2015/05/11 [received] PHST- 2015/08/10 [revised] PHST- 2015/09/13 [accepted] PHST- 2015/09/18 [aheadofprint] AID - S0145-2126(15)30385-4 [pii] AID - 10.1016/j.leukres.2015.09.014 [doi] PST - ppublish SO - Leuk Res. 2015 Dec;39(12):1353-9. doi: 10.1016/j.leukres.2015.09.014. Epub 2015 Sep 18. PMID- 26429297 OWN - NLM STAT- MEDLINE DA - 20151107 DCOM- 20160310 IS - 1474-5488 (Electronic) IS - 1470-2045 (Linking) VI - 16 IP - 15 DP - 2015 Nov TI - Busulfan plus cyclophosphamide versus busulfan plus fludarabine as a preparative regimen for allogeneic haemopoietic stem-cell transplantation in patients with acute myeloid leukaemia: an open-label, multicentre, randomised, phase 3 trial. PG - 1525-36 LID - 10.1016/S1470-2045(15)00200-4 [doi] LID - S1470-2045(15)00200-4 [pii] AB - BACKGROUND: The standard busulfan-cyclophosphamide myeloablative conditioning regimen is associated with substantial non-relapse mortality in patients older than 40 years with acute myeloid leukaemia who are undergoing allogeneic stem-cell transplantation. Because the combination of busulfan plus fludarabine has been proposed to reduce non-relapse mortality, we aimed to compare this treatment with busulfan plus cyclophosphamide as a preparative regimen in these patients. METHODS: We did an open-label, multicentre, randomised, phase 3 trial for patients with acute myeloid leukaemia at 25 hospital transplant centres in Italy and one in Israel. Eligible patients were aged 40-65 years, had an Eastern Cooperative Oncology Group performance status less than 3, and were in complete remission. Patients were randomly assigned 1:1 to receive intravenous busulfan plus cyclophosphamide or busulfan plus fludarabine. Treatment allocations were not masked to investigators or patients. Randomisation was done centrally via a dedicated web-based system using remote data entry, with patients stratified by donor type and complete remission status. Patients allocated to busulfan plus cyclophosphamide received intravenous busulfan 0.8 mg/kg four times per day during 2 h infusions for four consecutive days (16 doses from days -9 through -6; total dose 12.8 mg/kg) and cyclophosphamide at 60 mg/kg per day for two consecutive days (on days -4 and -3; total dose 120 mg/kg). Patients allocated to busulfan plus fludarabine received the same dose of intravenous busulfan (from days -6 through -3) and fludarabine at 40 mg/m(2) per day for four consecutive days (from days -6 through -3; total dose 160 mg/m(2)). The primary endpoint was 1-year non-relapse mortality, which was assessed on an intention-to-treat basis; safety outcomes were assessed in the per-protocol population. This trial has been completed and is registered with ClinicalTrials.gov, number NCT01191957. FINDINGS: Between Jan 3, 2008, and Dec 20, 2012, we enrolled and randomly assigned 252 patients to receive busulfan plus cyclophosphamide (n=125) or busulfan plus fludarabine (n=127). Median follow-up was 27.5 months (IQR 9.8-44.3). 1-year non-relapse mortality was 17.2% (95% CI 11.6-25.4) in the busulfan plus cyclophosphamide group and 7.9% (4.3-14.3) in the busulfan plus fludarabine group (Gray's test p=0.026). The most frequently reported grade 3 or higher adverse events were gastrointestinal events (28 [23%] of 121 patients in the busulfan plus cyclophosphamide group and 26 [21%] of 124 patients in the busulfan plus fludarabine group) and infections (21 [17%] patients in the busulfan plus cyclophosphamide group and 13 [10%] patients in the busulfan plus fludarabine group had at least one such event). INTERPRETATION: In older patients with acute myeloid leukaemia, the myeloablative busulfan plus fludarabine conditioning regimen is associated with lower transplant-related mortality than busulfan plus cyclophosphamide, but retains potent antileukaemic activity. Accordingly, this regimen should be regarded as standard of care during the planning of allogeneic transplants for such patients. FUNDING: Agenzia Italiana del Farmaco. CI - Copyright (c) 2015 Elsevier Ltd. All rights reserved. FAU - Rambaldi, Alessandro AU - Rambaldi A AD - Hematology and Bone Marrow Transplant Unit, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy. Electronic address: arambaldi@hpg23.it. FAU - Grassi, Anna AU - Grassi A AD - Hematology and Bone Marrow Transplant Unit, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy. FAU - Masciulli, Arianna AU - Masciulli A AD - Fondazione Mario Negri Sud, Santa Maria Imbaro, Italy. FAU - Boschini, Cristina AU - Boschini C AD - Hematology and Bone Marrow Transplant Unit, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy. FAU - Mico, Maria Caterina AU - Mico MC AD - Hematology and Bone Marrow Transplant Unit, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy. FAU - Busca, Alessandro AU - Busca A AD - Bone Marrow Transplant Unit, University of Torino, Turin, Italy. FAU - Bruno, Benedetto AU - Bruno B AD - Bone Marrow Transplant Unit, University of Torino, Turin, Italy. FAU - Cavattoni, Irene AU - Cavattoni I AD - Hematology and Bone Marrow Transplant Unit, Ospedale Centrale di Bolzano, Bolzano, Italy. FAU - Santarone, Stella AU - Santarone S AD - Bone Marrow Transplant Center, Ospedale Spirito Santo, Pescara, Italy. FAU - Raimondi, Roberto AU - Raimondi R AD - Hematology and Bone Marrow Transplant Unit, Ospedale San Bortolo, Vicenza, Italy. FAU - Montanari, Mauro AU - Montanari M AD - Hematology, Azienda Ospedali Riuniti, Ancona, Italy. FAU - Milone, Giuseppe AU - Milone G AD - Hematology and Bone Marrow Transplant Unit, Azienda Policlinico-Vittorio Emanuele, Catania, Italy. FAU - Chiusolo, Patrizia AU - Chiusolo P AD - Unit of Hematology, Policlinico Universitario A Gemelli, Rome, Italy. FAU - Pastore, Domenico AU - Pastore D AD - Department of Emergency and Organ Transplantation, Section of Hematology with Transplantation, Medical School, University of Bari, Bari, Italy. FAU - Guidi, Stefano AU - Guidi S AD - Department of Hematology, Bone Marrow Transplant Unit, University of Firenze, Florence, Italy. FAU - Patriarca, Francesca AU - Patriarca F AD - Hematology and Bone Marrow Transplant Unit, Azienda Ospedaliero Universitaria Ospedale Santa Maria della Misericordia di Udine, Udine, Italy. FAU - Risitano, Antonio M AU - Risitano AM AD - Hematology, AOU Federico II, Naples, Italy. FAU - Saporiti, Giorgia AU - Saporiti G AD - Hematology-Bone Marrow Transplant Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy. FAU - Pini, Massimo AU - Pini M AD - Hematology, AO SS Antonio e Biagio e C Arrigo, Alessandria, Italy. FAU - Terruzzi, Elisabetta AU - Terruzzi E AD - Hematology and Bone Marrow Transplant Unit, Azienda ospedaliera San Gerardo, Monza, Italy. FAU - Arcese, William AU - Arcese W AD - Hematology Division-Stem Cell Transplant Unit, Policlinico Tor Vergata, Rome, Italy. FAU - Marotta, Giuseppe AU - Marotta G AD - Department of Oncology, UOSA Transplant and Cellular Therapy Center, Azienda Ospedaliera Universitaria Senese, Siena, Italy. FAU - Carella, Angelo Michele AU - Carella AM AD - Hematology and Bone Marrow Transplant Unit, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy. FAU - Nagler, Arnon AU - Nagler A AD - Division of Hematology Bone Marrow Transplant & CBB, Chaim Sheba Medical Center, Tel Hashomer, Israel. FAU - Russo, Domenico AU - Russo D AD - Unit of Blood Diseases and Stem Cell Transplantation, Department of Clinical and Experimental Sciences, University of Brescia, Spedali Civili of Brescia, Brescia, Italy. FAU - Corradini, Paolo AU - Corradini P AD - Hematology and Bone Marrow Transplant Unit, Fondazione IRCCS Istituto Nazionale Tumori and University of Milano, Milan, Italy. FAU - Alessandrino, Emilio Paolo AU - Alessandrino EP AD - Department of Hematology Oncology, IRCCS Fondazione Policlinico San Matteo & University of Pavia, Pavia, Italy. FAU - Torelli, Giovanni Fernando AU - Torelli GF AD - Department of Cellular Biotechnologies and Hematology, Sapienza University, Rome, Italy. FAU - Scime, Rosanna AU - Scime R AD - Bone Marrow Transplant Unit, AOR Villa Sofia-Cervello, Palermo, Italy. FAU - Mordini, Nicola AU - Mordini N AD - Hematology, Azienda Ospedaliera S Croce e Carle, Cuneo, Italy. FAU - Oldani, Elena AU - Oldani E AD - Hematology and Bone Marrow Transplant Unit, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy. FAU - Marfisi, Rosa Maria AU - Marfisi RM AD - Fondazione Mario Negri Sud, Santa Maria Imbaro, Italy. FAU - Bacigalupo, Andrea AU - Bacigalupo A AD - Department of Hematology and Oncology, IRCCS AOU San Martino-IST, Genoa, Italy. FAU - Bosi, Alberto AU - Bosi A AD - Department of Hematology, Bone Marrow Transplant Unit, University of Firenze, Florence, Italy. LA - eng SI - ClinicalTrials.gov/NCT01191957 PT - Clinical Trial, Phase III PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20150928 PL - England TA - Lancet Oncol JT - The Lancet. Oncology JID - 100957246 RN - 0 (Antineoplastic Agents) RN - 8N3DW7272P (Cyclophosphamide) RN - FA2DM6879K (Vidarabine) RN - G1LN9045DK (Busulfan) RN - P2K93U8740 (fludarabine) SB - IM CIN - Lancet Oncol. 2015 Nov;16(15):1448-9. PMID: 26545834 MH - Adult MH - Aged MH - Antineoplastic Agents/*administration & dosage MH - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use MH - Busulfan/*administration & dosage MH - Cyclophosphamide/*administration & dosage MH - Female MH - *Hematopoietic Stem Cell Transplantation MH - Humans MH - *Induction Chemotherapy MH - Leukemia, Myeloid, Acute/*drug therapy/*surgery MH - Male MH - Middle Aged MH - *Transplantation Conditioning MH - Transplantation, Homologous MH - Vidarabine/administration & dosage/*analogs & derivatives EDAT- 2015/10/03 06:00 MHDA- 2016/03/11 06:00 CRDT- 2015/10/03 06:00 PHST- 2015/06/24 [received] PHST- 2015/07/22 [revised] PHST- 2015/07/24 [accepted] PHST- 2015/09/28 [aheadofprint] AID - S1470-2045(15)00200-4 [pii] AID - 10.1016/S1470-2045(15)00200-4 [doi] PST - ppublish SO - Lancet Oncol. 2015 Nov;16(15):1525-36. doi: 10.1016/S1470-2045(15)00200-4. Epub 2015 Sep 28. PMID- 26423235 OWN - NLM STAT- MEDLINE DA - 20151125 DCOM- 20160310 IS - 1873-5835 (Electronic) IS - 0145-2126 (Linking) VI - 39 IP - 12 DP - 2015 Dec TI - A new classification of interphase nuclei based on spatial organizations of chromosome 8 and 21 for t(8;21) (q22;q22) acute myeloid leukemia by three-dimensional fluorescence in situ hybridization. PG - 1414-20 LID - 10.1016/j.leukres.2015.09.013 [doi] LID - S0145-2126(15)30384-2 [pii] AB - Interphase heterogenous chromosomes spatially close to each other are predominantly located near the center of nuclei and are prone to incur translocations. We screened a t(8;21) (q22;q22) acute myeloid leukemia-M2 patient during three phases (post-chemotherapy, remittent stage, and relapse) and a donor of normal karyotype as control by two-(2D) and three-dimensional (3D)-fluorescence in situ hybridization (FISH). Our classification of nuclei (normal, transitional, and malignant nuclei) by 3D-FISH analyses may provide a more precise prognosis than 2D-FISH results, especially for remittent stage sample in our study, in which 2D-FISH findings showed normal results, whereas 3D-FISH results showed extreme abnormalities (normal nuclei 27%, transitional nuclei 36%, malignant nuclei 37%). The relative radial positions (d/R) of chromosomes 8 were similar to d/R of chromosomes 21 for the relapse sample. We classified heterogenous chromosome pairs into close pairs and normal pairs based on their relative distances (d'/(2R)). The centers of close pairs were more internal than normal pairs in nuclei in all samples, and the d/R values of a given-type pairwise heterogenous chromosomes were similar among four samples. Our data demonstrate that the classification of nuclei based on spatial organization of chromosomes by 3D-FISH is reasonable and essential for evaluating acute myeloid leukemia prognosis. CI - Copyright (c) 2015 Elsevier Ltd. All rights reserved. FAU - Tian, Xueli AU - Tian X AD - State Key Laboratory of Low-Dimensional Quantum Physics, Department of Physics, Tsinghua University, Beijing, China. FAU - Wang, Yanfang AU - Wang Y AD - Department of Hematology, Peking University Third Hospital, Beijing, China. FAU - Zhao, Fengying AU - Zhao F AD - State Key Laboratory of Low-Dimensional Quantum Physics, Department of Physics, Tsinghua University, Beijing, China. FAU - Liu, Jinlin AU - Liu J AD - Department of Automation, Tsinghua University, Beijing, China. FAU - Yin, Jun AU - Yin J AD - State Key Laboratory of Low-Dimensional Quantum Physics, Department of Physics, Tsinghua University, Beijing, China. FAU - Chen, Dieyan AU - Chen D AD - State Key Laboratory of Low-Dimensional Quantum Physics, Department of Physics, Tsinghua University, Beijing, China. FAU - Ma, Wanyun AU - Ma W AD - State Key Laboratory of Low-Dimensional Quantum Physics, Department of Physics, Tsinghua University, Beijing, China; Collaborative Innovation Center of Quantum Matter, Beijing, China. Electronic address: mawy@mail.tsinghua.edu.cn. FAU - Ke, Xiaoyan AU - Ke X AD - Department of Hematology, Peking University Third Hospital, Beijing, China. Electronic address: xiaoyank@yahoo.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150918 PL - England TA - Leuk Res JT - Leukemia research JID - 7706787 SB - IM MH - Bone Marrow Cells/ultrastructure MH - Cell Nucleus/*ultrastructure MH - Chromosomes, Human, Pair 21/*ultrastructure MH - Chromosomes, Human, Pair 8/*ultrastructure MH - Female MH - Humans MH - Immunophenotyping/*methods MH - In Situ Hybridization, Fluorescence/*methods MH - *Interphase MH - Leukemia, Myeloid, Acute/*genetics/mortality/pathology MH - Male MH - Prognosis MH - *Translocation, Genetic OTO - NOTNLM OT - 3D-FISH OT - Acute myeloid leukemia OT - Chromosome pair OT - Prognosis OT - Translocation EDAT- 2015/10/02 06:00 MHDA- 2016/03/11 06:00 CRDT- 2015/10/02 06:00 PHST- 2015/06/12 [received] PHST- 2015/08/17 [revised] PHST- 2015/09/13 [accepted] PHST- 2015/09/18 [aheadofprint] AID - S0145-2126(15)30384-2 [pii] AID - 10.1016/j.leukres.2015.09.013 [doi] PST - ppublish SO - Leuk Res. 2015 Dec;39(12):1414-20. doi: 10.1016/j.leukres.2015.09.013. Epub 2015 Sep 18. PMID- 26422556 OWN - NLM STAT- MEDLINE DA - 20151125 DCOM- 20160310 IS - 1873-5835 (Electronic) IS - 0145-2126 (Linking) VI - 39 IP - 12 DP - 2015 Dec TI - Reconstitution of lymphocyte subpopulations after hematopoietic stem cell transplantation: comparison of hematologic malignancies and donor types in event-free patients. PG - 1334-41 LID - 10.1016/j.leukres.2015.09.010 [doi] LID - S0145-2126(15)30381-7 [pii] AB - The reconstitution of different immunocyte subsets after hematopoietic stem cell transplantation (HSCT), follows different timelines. We prospectively investigated changes in lymphocyte subsets after HSCT and their associations with primary diagnosis, conditioning regimen, and HSCT type in event-free patients. A total of 95 patients (48 with acute myeloid leukemia, 22 with acute lymphoid leukemia, and 25 with myelodysplastic syndrome) who underwent allogeneic HSCT (34 sibling matched, 37 unrelated matched, and 24 haploidentical HSCT) but did not experience any events such as relapse or death were enrolled in this study. Lymphocyte subpopulations (T cells, helper/inducer T cells, cytotoxic/suppressor T cells, memory T cells, regulatory T cells, natural killer (NK) cells, NK-T cells, and B cells) were quantified by flow cytometry of peripheral blood from recipients 7 days before and 1, 2, 3, 6, and 12 months after HSCT. Leukocyte counts recovered within 1 month after HSCT. However, the number of T and B lymphocytes recovered at 2 months after HSCT. NK cell counts recovered shortly after haploidentical HSCT. However, T lymphocytes and their subpopulations showed delayed recovery after haploidentical HSCT. Lymphocyte subsets showed different sequential patterns according to HSCT type but no differences were seen according to primary diagnosis or conditioning regimen. CI - Copyright (c) 2015 Elsevier Ltd. All rights reserved. FAU - Park, Borae G AU - Park BG AD - Department of Laboratory Medicine, Asan Medical Center and University of Ulsan College of Medicine, Seoul, South Korea; Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, South Korea. FAU - Park, Chan-Jeoung AU - Park CJ AD - Department of Laboratory Medicine, Asan Medical Center and University of Ulsan College of Medicine, Seoul, South Korea. Electronic address: cjpark@amc.seoul.kr. FAU - Jang, Seongsoo AU - Jang S AD - Department of Laboratory Medicine, Asan Medical Center and University of Ulsan College of Medicine, Seoul, South Korea. FAU - Chi, Hyun-Sook AU - Chi HS AD - Department of Laboratory Medicine, Asan Medical Center and University of Ulsan College of Medicine, Seoul, South Korea. FAU - Kim, Dae-Young AU - Kim DY AD - Department of Internal Medicine, Asan Medical Center and University of Ulsan College of Medicine, Seoul, South Korea. FAU - Lee, Jung-Hee AU - Lee JH AD - Department of Internal Medicine, Asan Medical Center and University of Ulsan College of Medicine, Seoul, South Korea. FAU - Lee, Je-Hwan AU - Lee JH AD - Department of Internal Medicine, Asan Medical Center and University of Ulsan College of Medicine, Seoul, South Korea. FAU - Lee, Kyoo-Hyung AU - Lee KH AD - Department of Internal Medicine, Asan Medical Center and University of Ulsan College of Medicine, Seoul, South Korea. Electronic address: khlee2@amc.seoul.kr. LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150910 PL - England TA - Leuk Res JT - Leukemia research JID - 7706787 RN - 0 (Immunosuppressive Agents) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Allografts MH - Disease-Free Survival MH - Female MH - Flow Cytometry MH - Follow-Up Studies MH - Graft Survival MH - *Hematopoietic Stem Cell Transplantation MH - Histocompatibility MH - Humans MH - Immunophenotyping MH - Immunosuppressive Agents/therapeutic use MH - Leukemia, Myeloid, Acute/therapy MH - Living Donors MH - Lymphocyte Count MH - *Lymphocyte Subsets MH - Male MH - Middle Aged MH - Myelodysplastic Syndromes/therapy MH - Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy MH - Prospective Studies MH - Siblings MH - Transplantation Conditioning MH - Young Adult OTO - NOTNLM OT - Haploidentical stem cell transplantation OT - Hematopoietic stem cell transplantation OT - Immune reconstitution OT - Lymphocyte subpopulation EDAT- 2015/10/01 06:00 MHDA- 2016/03/11 06:00 CRDT- 2015/10/01 06:00 PHST- 2015/04/09 [received] PHST- 2015/08/09 [revised] PHST- 2015/09/07 [accepted] PHST- 2015/09/10 [aheadofprint] AID - S0145-2126(15)30381-7 [pii] AID - 10.1016/j.leukres.2015.09.010 [doi] PST - ppublish SO - Leuk Res. 2015 Dec;39(12):1334-41. doi: 10.1016/j.leukres.2015.09.010. Epub 2015 Sep 10. PMID- 26403986 OWN - NLM STAT- MEDLINE DA - 20151125 DCOM- 20160310 IS - 1873-5835 (Electronic) IS - 0145-2126 (Linking) VI - 39 IP - 12 DP - 2015 Dec TI - Reduced medical costs and hospital days when using oral arsenic plus ATRA as the first-line treatment of acute promyelocytic leukemia. PG - 1319-24 LID - 10.1016/j.leukres.2015.09.007 [doi] LID - S0145-2126(15)30376-3 [pii] AB - We have demonstrated that oral arsenic (Realgar-Indigo naturalis formula, RIF) plus all-trans retinoic acid (ATRA) is not inferior to intravenous arsenic trioxide (ATO) plus ATRA as the first-line treatment of acute promyelocytic leukemia (APL). To compare the cost-effectiveness of oral and intravenous arsenic, we analyzed the results of 30 patients in each group involved in a randomized controlled trial at our center. The median total medical costs were $13,183.49 in the RIF group compared with $24136.98 in the ATO group (p<0.0001). This difference primarily resulted from the different costs of induction therapy (p=0.016) and maintenance treatment (p<0.0001). The length of hospitalization for the RIF group was significantly lower than that for the ATO group (24 vs. 31 days, p<0.0001) during induction therapy. During maintenance treatment, the estimated medical costs were $2047.14 for each patient in the RIF group treated at home compared with $11273.81 for each patient in the ATO group treated in an outpatient setting (p<0.0001). We conclude that oral RIF plus ATRA significantly reduced the medical costs and length of hospital stay during induction and remission therapy compared with ATO plus ATRA in APL patients. CI - Copyright (c) 2015 Elsevier Ltd. All rights reserved. FAU - Jiang, Hao AU - Jiang H AD - Peking University People's Hospital, Peking University Institute of Hematology, Beijing 100044, China. FAU - Liang, Gong-Wen AU - Liang GW AD - Department of Pharmacy Administration and Clinical Pharmacy, Peking University Health Science Center, Beijing 100191, China. FAU - Huang, Xiao-Jun AU - Huang XJ AD - Peking University People's Hospital, Peking University Institute of Hematology, Beijing 100044, China. FAU - Jiang, Qian AU - Jiang Q AD - Peking University People's Hospital, Peking University Institute of Hematology, Beijing 100044, China. FAU - Han, Sheng AU - Han S AD - Department of Pharmacy Administration and Clinical Pharmacy, Peking University Health Science Center, Beijing 100191, China. FAU - Shi, Lu-Wen AU - Shi LW AD - Department of Pharmacy Administration and Clinical Pharmacy, Peking University Health Science Center, Beijing 100191, China. Electronic address: shilu@bjmu.edu.cn. FAU - Zhu, Hong-Hu AU - Zhu HH AD - Peking University People's Hospital, Peking University Institute of Hematology, Beijing 100044, China. Electronic address: zhuhhdoc@163.com. LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150909 PL - England TA - Leuk Res JT - Leukemia research JID - 7706787 RN - 0 (Arsenicals) RN - 0 (Oxides) RN - 5688UTC01R (Tretinoin) RN - S7V92P67HO (arsenic trioxide) SB - IM MH - Adolescent MH - Adult MH - Antineoplastic Combined Chemotherapy Protocols/*economics/therapeutic use MH - Arsenicals/administration & dosage/economics MH - China MH - Cost Savings MH - Cost-Benefit Analysis MH - Direct Service Costs MH - Female MH - Health Care Costs MH - Hospitals, University/economics MH - Humans MH - Length of Stay/economics/statistics & numerical data MH - Leukemia, Promyelocytic, Acute/*drug therapy/economics MH - Maintenance Chemotherapy/economics MH - Male MH - Middle Aged MH - Oxides/administration & dosage/economics MH - Remission Induction MH - Retrospective Studies MH - Tretinoin/administration & dosage/economics MH - Young Adult OTO - NOTNLM OT - Acute promyelocytic leukemia OT - Arsenic OT - Medical costs OT - Retinoic acid EDAT- 2015/09/26 06:00 MHDA- 2016/03/11 06:00 CRDT- 2015/09/26 06:00 PHST- 2015/04/12 [received] PHST- 2015/08/15 [revised] PHST- 2015/09/06 [accepted] PHST- 2015/09/09 [aheadofprint] AID - S0145-2126(15)30376-3 [pii] AID - 10.1016/j.leukres.2015.09.007 [doi] PST - ppublish SO - Leuk Res. 2015 Dec;39(12):1319-24. doi: 10.1016/j.leukres.2015.09.007. Epub 2015 Sep 9. PMID- 26392596 OWN - NLM STAT- MEDLINE DA - 20151120 DCOM- 20160303 IS - 1528-0020 (Electronic) IS - 0006-4971 (Linking) VI - 126 IP - 21 DP - 2015 Nov 19 TI - Targeted sequencing identifies patients with preclinical MDS at high risk of disease progression. PG - 2362-5 LID - 10.1182/blood-2015-08-663237 [doi] AB - The diagnosis of myelodysplastic syndromes (MDS) remains problematic due to the subjective nature of morphologic assessment. The reported high frequency of somatic mutations and increased structural variants by array-based cytogenetics have provided potential objective markers of disease; however, this has been complicated by reports of similar abnormalities in the healthy population. We aimed to identify distinguishing features between those with early MDS and reported healthy individuals by characterizing 69 patients who, following a nondiagnostic marrow, developed progressive dysplasia or acute myeloid leukemia. Targeted sequencing and array-based cytogenetics identified a driver mutation and/or structural variant in 91% (63/69) of prediagnostic samples with the mutational spectrum mirroring that in the MDS population. When compared with the reported healthy population, the mutations detected had significantly greater median variant allele fraction (40% vs 9% to 10%), and occurred more commonly with additional mutations (>/=2 mutations, 64% vs 8%). Furthermore, mutational analysis identified a high-risk group of patients with a shorter time to disease progression and poorer overall survival. The mutational features in our cohort are distinct from those seen in the healthy population and, even in the absence of definitive disease, can predict outcome. Early detection may allow consideration of intervention in poor-risk patients. CI - (c) 2015 by The American Society of Hematology. FAU - Cargo, Catherine A AU - Cargo CA AD - Haematological Malignancy Diagnostic Service, St James's University Hospital, Leeds, United Kingdom; FAU - Rowbotham, Nicola AU - Rowbotham N AD - Haematological Malignancy Diagnostic Service, St James's University Hospital, Leeds, United Kingdom; FAU - Evans, Paul A AU - Evans PA AD - Haematological Malignancy Diagnostic Service, St James's University Hospital, Leeds, United Kingdom; FAU - Barrans, Sharon L AU - Barrans SL AD - Haematological Malignancy Diagnostic Service, St James's University Hospital, Leeds, United Kingdom; FAU - Bowen, David T AU - Bowen DT AD - St James's Institute of Oncology, Leeds Teaching Hospitals, Leeds, United Kingdom; and. FAU - Crouch, Simon AU - Crouch S AD - Epidemiology and Cancer Statistics Group, University of York, York, United Kingdom. FAU - Jack, Andrew S AU - Jack AS AD - Haematological Malignancy Diagnostic Service, St James's University Hospital, Leeds, United Kingdom; LA - eng PT - Journal Article DEP - 20150921 PL - United States TA - Blood JT - Blood JID - 7603509 SB - AIM SB - IM CIN - Blood. 2015 Nov 19;126(21):2349-51. PMID: 26585803 MH - DNA Mutational Analysis MH - Disease-Free Survival MH - Female MH - Humans MH - Leukemia, Myeloid, Acute/*genetics/*mortality MH - Male MH - *Mutation MH - Myelodysplastic Syndromes/*genetics/*mortality MH - Retrospective Studies MH - Risk Factors MH - Survival Rate EDAT- 2015/09/24 06:00 MHDA- 2016/03/05 06:00 CRDT- 2015/09/23 06:00 PHST- 2015/08/07 [received] PHST- 2015/09/08 [accepted] PHST- 2015/09/21 [aheadofprint] AID - blood-2015-08-663237 [pii] AID - 10.1182/blood-2015-08-663237 [doi] PST - ppublish SO - Blood. 2015 Nov 19;126(21):2362-5. doi: 10.1182/blood-2015-08-663237. Epub 2015 Sep 21. PMID- 26377688 OWN - NLM STAT- MEDLINE DA - 20151113 DCOM- 20160229 IS - 1432-0851 (Electronic) IS - 0340-7004 (Linking) VI - 64 IP - 12 DP - 2015 Dec TI - RNA and protein expression of herpesvirus entry mediator (HVEM) is associated with molecular markers, immunity-related pathways and relapse-free survival of patients with AML. PG - 1505-15 LID - 10.1007/s00262-015-1755-8 [doi] AB - Immune checkpoint molecules are highly relevant as potential prognostic markers and therapeutic targets in malignant diseases. HVEM belongs to the TNF receptor family and provides stimulatory as well as inhibitory signals depending on the ligand. Abnormal HVEM expression has been described in various malignancies, but the role in AML is unknown. Here we report extensive data on HVEM surface protein expression analyzed by flow cytometry on bone marrow leukemic cells of 169 AML patients at diagnosis. An independent cohort of 512 AML patients was analyzed for HVEM mRNA expression in bone marrow samples by Affymetrix microarrays. Consistently for both cohorts and methods, we show that HVEM was differentially expressed and that expression levels were associated with defined genetic markers. HVEM expression was lower in cases with FLT3-ITD (p = 0.001, p < 0.001), with mutations in NPM1 (p = 0.001, p < 0.001) or with the combination of NPM1 mutation and FLT3 wild type (p = 0.049, p = 0.050), while a biallelic mutation in CEBPA correlated positively with higher HVEM expression (p = 0.015, p < 0.001). In a differential gene expression analysis, we found 13 genes including HOXA9, MEIS1 and MN1 that were closely associated with HVEM expression. Besides, four gene sets closely linked to immunity were enriched in HVEM (high) samples. Finally, high expression of HVEM was associated with a trend toward longer relapse-free survival. The results of this study provide new information on the potential significance of HVEM in AML. FAU - Lichtenegger, Felix S AU - Lichtenegger FS AD - Department of Internal Medicine III, Klinikum der Universitat Munchen, Marchioninistrasse 15, 81377, Munich, Germany. Felix.Lichtenegger@med.uni-muenchen.de. AD - Clinical Cooperation Group Immunotherapy, Helmholtz Zentrum Munchen, Munich, Germany. Felix.Lichtenegger@med.uni-muenchen.de. AD - Division of Clinical Pharmacology, Department of Internal Medicine IV, Klinikum der Universitat Munchen, Munich, Germany. Felix.Lichtenegger@med.uni-muenchen.de. FAU - Kondla, Isabell AU - Kondla I AD - Department of Internal Medicine III, Klinikum der Universitat Munchen, Marchioninistrasse 15, 81377, Munich, Germany. AD - Clinical Cooperation Group Immunotherapy, Helmholtz Zentrum Munchen, Munich, Germany. FAU - Krempasky, Michael AU - Krempasky M AD - Department of Internal Medicine III, Klinikum der Universitat Munchen, Marchioninistrasse 15, 81377, Munich, Germany. AD - Clinical Cooperation Group Immunotherapy, Helmholtz Zentrum Munchen, Munich, Germany. FAU - Weber, Anna L AU - Weber AL AD - Department of Internal Medicine III, Klinikum der Universitat Munchen, Marchioninistrasse 15, 81377, Munich, Germany. AD - Clinical Cooperation Group Immunotherapy, Helmholtz Zentrum Munchen, Munich, Germany. FAU - Herold, Tobias AU - Herold T AD - Department of Internal Medicine III, Klinikum der Universitat Munchen, Marchioninistrasse 15, 81377, Munich, Germany. AD - Clinical Cooperation Group Pathogenesis of Acute Leukemia, Helmholtz Zentrum Munchen, Munich, Germany. FAU - Krupka, Christina AU - Krupka C AD - Department of Internal Medicine III, Klinikum der Universitat Munchen, Marchioninistrasse 15, 81377, Munich, Germany. AD - Clinical Cooperation Group Immunotherapy, Helmholtz Zentrum Munchen, Munich, Germany. FAU - Spiekermann, Karsten AU - Spiekermann K AD - Department of Internal Medicine III, Klinikum der Universitat Munchen, Marchioninistrasse 15, 81377, Munich, Germany. AD - Clinical Cooperation Group Pathogenesis of Acute Leukemia, Helmholtz Zentrum Munchen, Munich, Germany. FAU - Schneider, Stephanie AU - Schneider S AD - Department of Internal Medicine III, Klinikum der Universitat Munchen, Marchioninistrasse 15, 81377, Munich, Germany. FAU - Buchner, Thomas AU - Buchner T AD - Department of Medicine A, Westfalische Wilhelms-Universitat Munster, Munster, Germany. FAU - Berdel, Wolfgang E AU - Berdel WE AD - Department of Medicine A, Westfalische Wilhelms-Universitat Munster, Munster, Germany. FAU - Wormann, Bernhard J AU - Wormann BJ AD - German Society of Hematology and Oncology, Berlin, Germany. FAU - Hiddemann, Wolfgang AU - Hiddemann W AD - Department of Internal Medicine III, Klinikum der Universitat Munchen, Marchioninistrasse 15, 81377, Munich, Germany. AD - Clinical Cooperation Group Pathogenesis of Acute Leukemia, Helmholtz Zentrum Munchen, Munich, Germany. FAU - Subklewe, Marion AU - Subklewe M AD - Department of Internal Medicine III, Klinikum der Universitat Munchen, Marchioninistrasse 15, 81377, Munich, Germany. AD - Clinical Cooperation Group Immunotherapy, Helmholtz Zentrum Munchen, Munich, Germany. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150916 PL - Germany TA - Cancer Immunol Immunother JT - Cancer immunology, immunotherapy : CII JID - 8605732 RN - 0 (Biomarkers, Tumor) RN - 0 (Receptors, Tumor Necrosis Factor, Member 14) RN - 63231-63-0 (RNA) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Biomarkers, Tumor/*genetics MH - Bone Marrow/metabolism MH - Disease-Free Survival MH - Female MH - Flow Cytometry MH - *Gene Expression Regulation, Neoplastic MH - Humans MH - Leukemia, Myeloid, Acute/diagnosis/*genetics/immunology/mortality MH - Male MH - Middle Aged MH - RNA/genetics MH - Receptors, Tumor Necrosis Factor, Member 14/*genetics/immunology OTO - NOTNLM OT - Acute myeloid leukemia (AML) OT - Costimulation OT - Gene expression analysis OT - Herpesvirus entry mediator (HVEM) OT - Immune checkpoint molecules OT - Immunophenotyping EDAT- 2015/09/18 06:00 MHDA- 2016/03/02 06:00 CRDT- 2015/09/18 06:00 PHST- 2014/10/29 [received] PHST- 2015/09/04 [accepted] PHST- 2015/09/16 [aheadofprint] AID - 10.1007/s00262-015-1755-8 [doi] AID - 10.1007/s00262-015-1755-8 [pii] PST - ppublish SO - Cancer Immunol Immunother. 2015 Dec;64(12):1505-15. doi: 10.1007/s00262-015-1755-8. Epub 2015 Sep 16. PMID- 26343130 OWN - NLM STAT- MEDLINE DA - 20151103 DCOM- 20160317 IS - 1873-4316 (Electronic) IS - 1389-2010 (Linking) VI - 17 IP - 1 DP - 2016 TI - The Past, Present and Future Subclassification of Patients with Acute Myeloid Leukemia. PG - 6-19 AB - Acute myeloid leukemia (AML) is characterized as a heterogeneous disease where the patients are sub grouped according to several classification systems and mutational analyses. Diagnosis of AML is based on identification of the specific myeloid cell initiating the disease, quantification of immature blasts in bone marrow and peripheral blood, as well as detection of mutations and translocations. The heterogeneity of AML is caused by a block in differentiation that may occur in any of the different myeloid cell populations. These undifferentiated cells also harbor an increased proliferation potential that leads to accumulation of immature leukemic cells. The current development of more sensitive and less labor intensive analysis methods has led classification of patients from being a system based on morphology of the leukemic cells to being more sophisticated, detecting translocations and small mutations found in the whole leukemic clone or in a minor subclone. This review aims to describe the most common classification systems of AML, including frequently occurring translocations, mutations and epigenetic alterations, as well as describe traditional and novel methods for diagnosis and analysis of these patients. FAU - Forthun, Rakel B AU - Forthun RB AD - Department of Clinical Science, Faculty of Medicine, University of Bergen, Jonas Lies veg 87, 5021 Bergen, Norway. Rakel.Forthun@k2.uib.no. FAU - Hinrichs, Carina AU - Hinrichs C FAU - Dowling, Tara H AU - Dowling TH FAU - Bruserud, Oystein AU - Bruserud O FAU - Selheim, Frode AU - Selheim F LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review PL - Netherlands TA - Curr Pharm Biotechnol JT - Current pharmaceutical biotechnology JID - 100960530 SB - IM MH - Cell Differentiation/genetics MH - Epigenesis, Genetic MH - Gene Expression Regulation, Neoplastic MH - Humans MH - Karyotyping MH - Leukemia, Myeloid, Acute/*genetics/pathology MH - Mutation MH - Transcriptome EDAT- 2015/09/08 06:00 MHDA- 2016/03/18 06:00 CRDT- 2015/09/08 06:00 PHST- 2014/04/20 [received] PHST- 2015/06/18 [revised] PHST- 2015/07/22 [accepted] AID - CPB-EPUB-70203 [pii] PST - ppublish SO - Curr Pharm Biotechnol. 2016;17(1):6-19. PMID- 26340914 OWN - NLM STAT- MEDLINE DA - 20151125 DCOM- 20160310 IS - 1873-5835 (Electronic) IS - 0145-2126 (Linking) VI - 39 IP - 12 DP - 2015 Dec TI - The impact of standard chemotherapy on miRNA signature in plasma in AML patients. PG - 1389-95 LID - 10.1016/j.leukres.2015.08.009 [doi] LID - S0145-2126(15)30362-3 [pii] AB - AIM: In our pilot study, we used plasma samples as liquid biopsy to search for miRNA signatures in patients with acute myeloid leukemia (AML) at diagnosis and in remission achieved after standard chemotherapy before planned transplantation. MATERIAL AND METHODS: We examined 10 plasma samples from healthy volunteers and 8 paired samples from patients with AML at diagnosis and in remission using TaqMan MicroRNA Arrays. The results were validated using single-target qPCR reactions run in triplicates. RESULTS: We selected 6 miRNAs with expressions significantly sensitive to therapy: miR-199b-5p, miR-301b, miR-326, miR-361-5p, miR-625 and miR-655. All selected miRNAs were not or very weakly expressed in healthy individuals. They were abundant in plasma in patients at diagnosis but their levels decreased after chemotherapy. CONCLUSION: We detected a therapy sensitive miRNA signature in plasma of patients with AML. CI - Copyright (c) 2015 Elsevier Ltd. All rights reserved. FAU - Koutova, Linda AU - Koutova L AD - Department of Hematoonocology, Charles University Hospital in Pilsen, Alej Svobody 80, 304 60 Pilsen, Czech Republic. FAU - Sterbova, Monika AU - Sterbova M AD - Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University in Prague and General Faculty Hospital in Prague, Albertov 4, 128 00 Prague, Czech Republic. FAU - Pazourkova, Eva AU - Pazourkova E AD - Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University in Prague and General Faculty Hospital in Prague, Albertov 4, 128 00 Prague, Czech Republic. FAU - Pospisilova, Sarka AU - Pospisilova S AD - Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University in Prague and General Faculty Hospital in Prague, Albertov 4, 128 00 Prague, Czech Republic. FAU - Svobodova, Iveta AU - Svobodova I AD - Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University in Prague and General Faculty Hospital in Prague, Albertov 4, 128 00 Prague, Czech Republic. FAU - Horinek, Ales AU - Horinek A AD - Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University in Prague and General Faculty Hospital in Prague, Albertov 4, 128 00 Prague, Czech Republic. FAU - Lysak, Daniel AU - Lysak D AD - Department of Hematoonocology, Charles University Hospital in Pilsen, Alej Svobody 80, 304 60 Pilsen, Czech Republic. FAU - Korabecna, Marie AU - Korabecna M AD - Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University in Prague and General Faculty Hospital in Prague, Albertov 4, 128 00 Prague, Czech Republic; Medical Faculty in Pilsen, Charles University in Prague, Husova 3, 306 05 Pilsen, Czech Republic. Electronic address: marie.korabecna@lf1.cuni.cz. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Validation Studies DEP - 20150820 PL - England TA - Leuk Res JT - Leukemia research JID - 7706787 RN - 0 (MIRN301 microRNA, human) RN - 0 (MIRN326 microRNA, human) RN - 0 (MIRN361 microRNA, human) RN - 0 (MIRN625 microRNA, human) RN - 0 (MIRN655 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (RNA, Neoplasm) RN - 0 (mirn199 microRNA, human) RN - 04079A1RDZ (Cytarabine) RN - BZ114NVM5P (Mitoxantrone) RN - ZRP63D75JW (Idarubicin) SB - IM CIN - Leuk Res. 2015 Dec;39(12):1309-11. PMID: 26602021 MH - Adult MH - Antineoplastic Combined Chemotherapy Protocols/*pharmacology/therapeutic use MH - Consolidation Chemotherapy MH - Cytarabine/administration & dosage MH - Female MH - Gene Expression Regulation, Leukemic/*drug effects MH - Humans MH - Idarubicin/administration & dosage MH - Leukemia, Myeloid, Acute/blood/*drug therapy/genetics MH - Male MH - MicroRNAs/biosynthesis/*blood/genetics MH - Middle Aged MH - Mitoxantrone/administration & dosage MH - Pilot Projects MH - RNA, Neoplasm/biosynthesis/*blood/genetics MH - Real-Time Polymerase Chain Reaction MH - Remission Induction MH - *Transcriptome OTO - NOTNLM OT - Acute myeloid leukemia OT - Liquid biopsy OT - Plasma OT - Remission OT - Standard chemotherapy OT - miRNA signature EDAT- 2015/09/06 06:00 MHDA- 2016/03/11 06:00 CRDT- 2015/09/06 06:00 PHST- 2014/10/11 [received] PHST- 2015/07/22 [revised] PHST- 2015/08/15 [accepted] PHST- 2015/08/20 [aheadofprint] AID - S0145-2126(15)30362-3 [pii] AID - 10.1016/j.leukres.2015.08.009 [doi] PST - ppublish SO - Leuk Res. 2015 Dec;39(12):1389-95. doi: 10.1016/j.leukres.2015.08.009. Epub 2015 Aug 20. PMID- 26304885 OWN - NLM STAT- MEDLINE DA - 20151030 DCOM- 20160314 IS - 1527-7755 (Electronic) IS - 0732-183X (Linking) VI - 33 IP - 31 DP - 2015 Nov 1 TI - Epidemiology and Clinical Significance of Secondary and Therapy-Related Acute Myeloid Leukemia: A National Population-Based Cohort Study. PG - 3641-9 LID - 10.1200/JCO.2014.60.0890 [doi] AB - PURPOSE: Secondary and therapy-related acute myeloid leukemia (sAML and tAML, respectively) remain therapeutic challenges. Still, it is unclear whether their inferior outcome compared with de novo acute myeloid leukemia (AML) varies as a result of previous hematologic disease or can be explained by differences in karyotype and/or age. PATIENTS AND METHODS: In a Danish national population-based study of 3,055 unselected patients with AML diagnosed from 2000 to 2013, we compared the frequencies and characteristics of tAML, myelodysplastic syndrome (MDS) -sAML, and non-MDS-sAML (chronic myelomonocytic leukemia and myeloproliferative neoplasia) versus de novo AML. Limited to intensive therapy patients, we compared chance of complete remission by logistic regression analysis and used a pseudo-value approach to compare relative risk (RR) of death at 90 days, 1 year, and 3 years, overall and stratified by age and karyotype. Results were given crude and adjusted with 95% CIs. RESULTS: Overall, frequencies of sAML and tAML were 19.8% and 6.6%, respectively. sAML, but not tAML, was associated with low likelihood of receiving intensive treatment. Among intensive therapy patients (n = 1,567), antecedent myeloid disorder or prior cytotoxic exposure was associated with decreased complete remission rates and inferior survival (3-year adjusted RR for MDS-sAML, non-MDS-sAML, and tAML: RR, 1.14; 95% CI, 1.02 to 1.32; RR, 1.27; 95% CI, 1.16 to 1.34; and RR, 1.16; 95% CI, 1.03 to 1.32, respectively) compared with de novo AML. Among patients >/= 60 years old and patients with adverse karyotype, previous MDS or tAML did not impact overall outcomes, whereas non-MDS-sAML was associated with inferior survival across age and cytogenetic risk groups (adverse risk cytogenetics: 1-year adjusted RR, 1.47; 95% CI, 1.23 to 1.76; patients >/= 60 years old: 1-year adjusted RR, 1.31; 95% CI, 1.06 to 1.61). CONCLUSION: Our results support that de novo AML, sAML, and tAML are biologically and prognostically distinct subtypes of AML. Patients with non-MDS-sAML have dismal outcomes, independent of age and cytogenetics. Previous myeloid disorder, age, and cytogenetics are crucial determinants of outcomes and should be integrated in treatment recommendations for these patients. CI - (c) 2015 by American Society of Clinical Oncology. FAU - Granfeldt Ostgard, Lene Sofie AU - Granfeldt Ostgard LS AD - Lene Sofie Granfeldt Ostgard, Mette Norgaard, Eigil Kjeldsen, and Jan Maxwell Norgaard, Aarhus University Hospital, Aarhus; Henrik Sengelov, Mette Klarskov Andersen, and Lone Smidstrup Friis, The University Hospital Rigshospitalet, Copenhagen; Inge Hogh Dufva, Herlev University Hospital, Herlev; Claus Werenberg Marcher and Birgitte Preiss, Odense University Hospital, Odense; Marianne Severinsen, Aalborg University Hospital, Aalborg, Denmark; and Bruno C. Medeiros, Stanford University School of Medicine, Stanford, CA. lenoestg@rm.dk. FAU - Medeiros, Bruno C AU - Medeiros BC AD - Lene Sofie Granfeldt Ostgard, Mette Norgaard, Eigil Kjeldsen, and Jan Maxwell Norgaard, Aarhus University Hospital, Aarhus; Henrik Sengelov, Mette Klarskov Andersen, and Lone Smidstrup Friis, The University Hospital Rigshospitalet, Copenhagen; Inge Hogh Dufva, Herlev University Hospital, Herlev; Claus Werenberg Marcher and Birgitte Preiss, Odense University Hospital, Odense; Marianne Severinsen, Aalborg University Hospital, Aalborg, Denmark; and Bruno C. Medeiros, Stanford University School of Medicine, Stanford, CA. FAU - Sengelov, Henrik AU - Sengelov H AD - Lene Sofie Granfeldt Ostgard, Mette Norgaard, Eigil Kjeldsen, and Jan Maxwell Norgaard, Aarhus University Hospital, Aarhus; Henrik Sengelov, Mette Klarskov Andersen, and Lone Smidstrup Friis, The University Hospital Rigshospitalet, Copenhagen; Inge Hogh Dufva, Herlev University Hospital, Herlev; Claus Werenberg Marcher and Birgitte Preiss, Odense University Hospital, Odense; Marianne Severinsen, Aalborg University Hospital, Aalborg, Denmark; and Bruno C. Medeiros, Stanford University School of Medicine, Stanford, CA. FAU - Norgaard, Mette AU - Norgaard M AD - Lene Sofie Granfeldt Ostgard, Mette Norgaard, Eigil Kjeldsen, and Jan Maxwell Norgaard, Aarhus University Hospital, Aarhus; Henrik Sengelov, Mette Klarskov Andersen, and Lone Smidstrup Friis, The University Hospital Rigshospitalet, Copenhagen; Inge Hogh Dufva, Herlev University Hospital, Herlev; Claus Werenberg Marcher and Birgitte Preiss, Odense University Hospital, Odense; Marianne Severinsen, Aalborg University Hospital, Aalborg, Denmark; and Bruno C. Medeiros, Stanford University School of Medicine, Stanford, CA. FAU - Andersen, Mette Klarskov AU - Andersen MK AD - Lene Sofie Granfeldt Ostgard, Mette Norgaard, Eigil Kjeldsen, and Jan Maxwell Norgaard, Aarhus University Hospital, Aarhus; Henrik Sengelov, Mette Klarskov Andersen, and Lone Smidstrup Friis, The University Hospital Rigshospitalet, Copenhagen; Inge Hogh Dufva, Herlev University Hospital, Herlev; Claus Werenberg Marcher and Birgitte Preiss, Odense University Hospital, Odense; Marianne Severinsen, Aalborg University Hospital, Aalborg, Denmark; and Bruno C. Medeiros, Stanford University School of Medicine, Stanford, CA. FAU - Dufva, Inge Hogh AU - Dufva IH AD - Lene Sofie Granfeldt Ostgard, Mette Norgaard, Eigil Kjeldsen, and Jan Maxwell Norgaard, Aarhus University Hospital, Aarhus; Henrik Sengelov, Mette Klarskov Andersen, and Lone Smidstrup Friis, The University Hospital Rigshospitalet, Copenhagen; Inge Hogh Dufva, Herlev University Hospital, Herlev; Claus Werenberg Marcher and Birgitte Preiss, Odense University Hospital, Odense; Marianne Severinsen, Aalborg University Hospital, Aalborg, Denmark; and Bruno C. Medeiros, Stanford University School of Medicine, Stanford, CA. FAU - Friis, Lone Smidstrup AU - Friis LS AD - Lene Sofie Granfeldt Ostgard, Mette Norgaard, Eigil Kjeldsen, and Jan Maxwell Norgaard, Aarhus University Hospital, Aarhus; Henrik Sengelov, Mette Klarskov Andersen, and Lone Smidstrup Friis, The University Hospital Rigshospitalet, Copenhagen; Inge Hogh Dufva, Herlev University Hospital, Herlev; Claus Werenberg Marcher and Birgitte Preiss, Odense University Hospital, Odense; Marianne Severinsen, Aalborg University Hospital, Aalborg, Denmark; and Bruno C. Medeiros, Stanford University School of Medicine, Stanford, CA. FAU - Kjeldsen, Eigil AU - Kjeldsen E AD - Lene Sofie Granfeldt Ostgard, Mette Norgaard, Eigil Kjeldsen, and Jan Maxwell Norgaard, Aarhus University Hospital, Aarhus; Henrik Sengelov, Mette Klarskov Andersen, and Lone Smidstrup Friis, The University Hospital Rigshospitalet, Copenhagen; Inge Hogh Dufva, Herlev University Hospital, Herlev; Claus Werenberg Marcher and Birgitte Preiss, Odense University Hospital, Odense; Marianne Severinsen, Aalborg University Hospital, Aalborg, Denmark; and Bruno C. Medeiros, Stanford University School of Medicine, Stanford, CA. FAU - Marcher, Claus Werenberg AU - Marcher CW AD - Lene Sofie Granfeldt Ostgard, Mette Norgaard, Eigil Kjeldsen, and Jan Maxwell Norgaard, Aarhus University Hospital, Aarhus; Henrik Sengelov, Mette Klarskov Andersen, and Lone Smidstrup Friis, The University Hospital Rigshospitalet, Copenhagen; Inge Hogh Dufva, Herlev University Hospital, Herlev; Claus Werenberg Marcher and Birgitte Preiss, Odense University Hospital, Odense; Marianne Severinsen, Aalborg University Hospital, Aalborg, Denmark; and Bruno C. Medeiros, Stanford University School of Medicine, Stanford, CA. FAU - Preiss, Birgitte AU - Preiss B AD - Lene Sofie Granfeldt Ostgard, Mette Norgaard, Eigil Kjeldsen, and Jan Maxwell Norgaard, Aarhus University Hospital, Aarhus; Henrik Sengelov, Mette Klarskov Andersen, and Lone Smidstrup Friis, The University Hospital Rigshospitalet, Copenhagen; Inge Hogh Dufva, Herlev University Hospital, Herlev; Claus Werenberg Marcher and Birgitte Preiss, Odense University Hospital, Odense; Marianne Severinsen, Aalborg University Hospital, Aalborg, Denmark; and Bruno C. Medeiros, Stanford University School of Medicine, Stanford, CA. FAU - Severinsen, Marianne AU - Severinsen M AD - Lene Sofie Granfeldt Ostgard, Mette Norgaard, Eigil Kjeldsen, and Jan Maxwell Norgaard, Aarhus University Hospital, Aarhus; Henrik Sengelov, Mette Klarskov Andersen, and Lone Smidstrup Friis, The University Hospital Rigshospitalet, Copenhagen; Inge Hogh Dufva, Herlev University Hospital, Herlev; Claus Werenberg Marcher and Birgitte Preiss, Odense University Hospital, Odense; Marianne Severinsen, Aalborg University Hospital, Aalborg, Denmark; and Bruno C. Medeiros, Stanford University School of Medicine, Stanford, CA. FAU - Norgaard, Jan Maxwell AU - Norgaard JM AD - Lene Sofie Granfeldt Ostgard, Mette Norgaard, Eigil Kjeldsen, and Jan Maxwell Norgaard, Aarhus University Hospital, Aarhus; Henrik Sengelov, Mette Klarskov Andersen, and Lone Smidstrup Friis, The University Hospital Rigshospitalet, Copenhagen; Inge Hogh Dufva, Herlev University Hospital, Herlev; Claus Werenberg Marcher and Birgitte Preiss, Odense University Hospital, Odense; Marianne Severinsen, Aalborg University Hospital, Aalborg, Denmark; and Bruno C. Medeiros, Stanford University School of Medicine, Stanford, CA. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150824 PL - United States TA - J Clin Oncol JT - Journal of clinical oncology : official journal of the American Society of Clinical Oncology JID - 8309333 RN - 0 (Antineoplastic Agents) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Aged, 80 and over MH - Antineoplastic Agents/*adverse effects MH - Cohort Studies MH - Denmark MH - Female MH - Hematologic Diseases/complications/drug therapy MH - Humans MH - Kaplan-Meier Estimate MH - Karyotyping MH - Leukemia, Myeloid, Acute/*chemically induced/*epidemiology MH - Male MH - Middle Aged MH - Myelodysplastic Syndromes/epidemiology/therapy MH - Myeloproliferative Disorders/epidemiology/therapy MH - Neoplasms/complications/drug therapy MH - Neoplasms, Second Primary/chemically induced/epidemiology MH - Prognosis MH - Registries MH - Regression Analysis MH - Remission Induction MH - Treatment Outcome MH - Young Adult EDAT- 2015/08/26 06:00 MHDA- 2016/03/15 06:00 CRDT- 2015/08/26 06:00 PHST- 2015/08/24 [aheadofprint] AID - JCO.2014.60.0890 [pii] AID - 10.1200/JCO.2014.60.0890 [doi] PST - ppublish SO - J Clin Oncol. 2015 Nov 1;33(31):3641-9. doi: 10.1200/JCO.2014.60.0890. Epub 2015 Aug 24. PMID- 26286093 OWN - NLM STAT- MEDLINE DA - 20150825 DCOM- 20160229 LR - 20151008 IS - 1179-1969 (Electronic) IS - 1170-229X (Linking) VI - 32 IP - 8 DP - 2015 Aug TI - Management of Relapsed/Refractory Acute Myeloid Leukemia in the Elderly: Current Strategies and Developments. PG - 623-37 LID - 10.1007/s40266-015-0285-6 [doi] AB - Elderly patients with acute myeloid leukemia (AML) who are refractory to or relapse following frontline treatment constitute a poor-risk group with a poor long-term outcome. Host-related factors and unfavorable disease-related features contribute to early treatment failures following frontline therapy, thus making attainment of remission and long-term survival with salvage therapy particularly challenging for elderly patients. Currently, no optimal salvage strategy exists for responding patients, and allogeneic hematopoietic stem cell transplant is the only curative option in this setting; however, the vast majority of elderly patients are not candidates for this procedure due to poor functional status secondary to age and age-related comorbidities. Furthermore, the lack of effective salvage programs available for elderly patients with recurrent AML underscores the need for therapies that consistently yield durable remissions or durable control of their disease. The purpose of this review was to highlight the currently available strategies, as well as future strategies under development, for treating older patients with recurrent AML. FAU - Bryan, Jeffrey C AU - Bryan JC AD - The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Jabbour, Elias J AU - Jabbour EJ LA - eng GR - P30 CA016672/CA/NCI NIH HHS/United States PT - Journal Article PT - Review PL - New Zealand TA - Drugs Aging JT - Drugs & aging JID - 9102074 SB - IM MH - Aged MH - Hematopoietic Stem Cell Transplantation/*methods MH - Humans MH - Leukemia, Myeloid, Acute/*therapy MH - Recurrence MH - Salvage Therapy/*methods MH - Treatment Outcome EDAT- 2015/08/20 06:00 MHDA- 2016/03/02 06:00 CRDT- 2015/08/20 06:00 AID - 10.1007/s40266-015-0285-6 [doi] PST - ppublish SO - Drugs Aging. 2015 Aug;32(8):623-37. doi: 10.1007/s40266-015-0285-6. PMID- 26278525 OWN - NLM STAT- MEDLINE DA - 20151103 DCOM- 20160317 IS - 1873-4316 (Electronic) IS - 1389-2010 (Linking) VI - 17 IP - 1 DP - 2016 TI - The Use of Nanocarriers in Acute Myeloid Leukaemia Therapy: Challenges and Current Status. PG - 30-41 AB - Chemotherapy for AML is hampered by severe side-effects and failure to eliminate all the blasts that eventually leads to relapse. The use of nanosized particulate drug carriers such as liposomes and polymeric nanoparticles has the potential to improve AML therapy by delivering more of the drug to the disease site, thereby reducing toxicity. For example, encapsulation in liposomes reduces the cardiotoxicity of anthracyclines, giving an improved therapeutic index. Moreover, when the surface properties are engineered appropriately, nanocarriers remain in the circulation and extravasate in tissues with sinusoidal capillaries, one of which is bone marrow, leading to a more favourable distribution of the associated drug. Drug carrier technology contributes to the development of newer drugs, such as nucleic acids that can be protected from degradation and delivered into cells, thus opening the way for gene-silencing strategies. Furthermore, carrier systems provide a means of dispersing poorly water-soluble molecule for in vivo administration and thus increase the "druggability" of new lead compounds, such as heat-shock protein inhibitors. Particulate carriers can transport more than one active agent, allowing synergistic action and theranostic strategies. Notably, phase I and II clinical trials are being performed with CPX-351, a liposomal formulation containing cytarabine and daunorubicin at an optimal ratio. Finally, by attaching suitable ligands to the nanocarrier surface, specific targeting to AML cells can be achieved. In this review, we give examples of successful targeting to folate and transferrin receptors against AML. FAU - Sauvage, Felix AU - Sauvage F FAU - Barratt, Gillian AU - Barratt G AD - Institut Galien Paris-Sud, Faculte de Pharmacie, 5 rue J.B. Clement Chatenay-Malabry, F92296 Cedex, France. gillian.barratt@u-psud.fr. FAU - Herfindal, Lars AU - Herfindal L FAU - Vergnaud-Gauduchon, Juliette AU - Vergnaud-Gauduchon J LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review PL - Netherlands TA - Curr Pharm Biotechnol JT - Current pharmaceutical biotechnology JID - 100960530 RN - 0 (Antineoplastic Agents) RN - 0 (Colloids) RN - 0 (Drug Carriers) SB - IM MH - Antineoplastic Agents/therapeutic use MH - Clinical Trials as Topic MH - Colloids MH - Drug Carriers/administration & dosage MH - Humans MH - Leukemia, Myeloid, Acute/*therapy MH - Nanoparticles/*administration & dosage EDAT- 2015/08/19 06:00 MHDA- 2016/03/18 06:00 CRDT- 2015/08/18 06:00 PHST- 2015/04/16 [received] PHST- 2015/06/08 [revised] PHST- 2015/07/23 [accepted] AID - CPB-EPUB-69546 [pii] PST - ppublish SO - Curr Pharm Biotechnol. 2016;17(1):30-41. PMID- 26185105 OWN - NLM STAT- MEDLINE DA - 20150718 DCOM- 20160310 LR - 20150721 IS - 1746-1596 (Electronic) IS - 1746-1596 (Linking) VI - 10 DP - 2015 TI - Low expression of circulating microRNA-328 is associated with poor prognosis in patients with acute myeloid leukemia. PG - 109 LID - 10.1186/s13000-015-0345-6 [doi] AB - BACKGROUND: Dysregulation of circulating miR-328 has been identified in several tumors and is associated with prognosis of patients. However, the expression pattern of miR-328 and the impact on prognosis has not yet been studied in acute myeloid leukemia (AML). The purpose of this study is to investigate the expression status of miR-328 and its clinical significance in AML patients. METHODS: RNA was extracted from plasma of 176 patients with newly diagnosed AML and 70 healthy volunteers. The miR-328 expression was examined by Realtime quantitative PCR. The association of circulating miR-328 expression with clinicopathological factors and prognosis of AML patients was statistically analyzed. RESULTS: The expression of miR-328 was significantly downregulated in AML patients (median value 22.99, range: 3.63-242.0) compared with those of healthy controls (median value 89.17, range: 12.05-397.7; P < 0.001), and miR-328 expression was markedly increased in patients after treatment than before (23.40 +/- 1.76 vs. 46.61 +/- 3.83, P < 0.001). Moreover, low levels of miR-328 were associated with a higher white blood cell count and BM blast count (P = 0.026 and P = 0.003, respectively), and lower hemoglobin and platelet count (P = 0.004 and P = 0.022, respectively). Patients with low miR-328 expression had a relatively poor overall survival (P = 0.022) and shorter relapse-free survival (P = 0.008) than those with high miR-328 expression. In addition, low miR-328 expression was an independent prognostic factors for both OS (P = 0.017) and RFS (P = 0.023). CONCLUSIONS: Circulating miR-328 downregulation is a common event and is associated with poor clinical outcome in AML patients. FAU - Liu, Li AU - Liu L AD - Department of Haematology, Tangdu Hospital, Fourth Military Medical University, No.1, Xinsi Road, Xi'an, Shaanxi, 710038, People's Republic of China. lliu6699@126.com. FAU - Chen, Ren'an AU - Chen R AD - Department of Haematology, Tangdu Hospital, Fourth Military Medical University, No.1, Xinsi Road, Xi'an, Shaanxi, 710038, People's Republic of China. FAU - Zhang, Yangping AU - Zhang Y AD - Department of Haematology, Tangdu Hospital, Fourth Military Medical University, No.1, Xinsi Road, Xi'an, Shaanxi, 710038, People's Republic of China. FAU - Fan, Wen AU - Fan W AD - Department of Haematology, Tangdu Hospital, Fourth Military Medical University, No.1, Xinsi Road, Xi'an, Shaanxi, 710038, People's Republic of China. FAU - Xiao, Fang AU - Xiao F AD - Department of Haematology, Tangdu Hospital, Fourth Military Medical University, No.1, Xinsi Road, Xi'an, Shaanxi, 710038, People's Republic of China. FAU - Yan, Xueqian AU - Yan X AD - Department of Haematology, Tangdu Hospital, Fourth Military Medical University, No.1, Xinsi Road, Xi'an, Shaanxi, 710038, People's Republic of China. LA - eng PT - Journal Article DEP - 20150717 PL - England TA - Diagn Pathol JT - Diagnostic pathology JID - 101251558 RN - 0 (Biomarkers, Tumor) RN - 0 (Hemoglobins) RN - 0 (MIRN328 microRNA, human) RN - 0 (MicroRNAs) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Biomarkers, Tumor/blood/*genetics MH - Case-Control Studies MH - Disease Progression MH - Disease-Free Survival MH - Down-Regulation MH - Female MH - Hemoglobins/metabolism MH - Humans MH - Kaplan-Meier Estimate MH - Leukemia, Myeloid, Acute/blood/diagnosis/*genetics/mortality/therapy MH - Leukocyte Count MH - Male MH - MicroRNAs/blood/*genetics MH - Middle Aged MH - Platelet Count MH - Real-Time Polymerase Chain Reaction MH - Reverse Transcriptase Polymerase Chain Reaction MH - Risk Factors MH - Time Factors MH - Treatment Outcome MH - Young Adult PMC - PMC4504459 OID - NLM: PMC4504459 EDAT- 2015/07/18 06:00 MHDA- 2016/03/11 06:00 CRDT- 2015/07/18 06:00 PHST- 2015/01/11 [received] PHST- 2015/07/09 [accepted] PHST- 2015/07/17 [aheadofprint] AID - 10.1186/s13000-015-0345-6 [doi] AID - 10.1186/s13000-015-0345-6 [pii] PST - epublish SO - Diagn Pathol. 2015 Jul 17;10:109. doi: 10.1186/s13000-015-0345-6. PMID- 26143266 OWN - NLM STAT- MEDLINE DA - 20150706 DCOM- 20160324 IS - 1534-6277 (Electronic) IS - 1534-6277 (Linking) VI - 16 IP - 8 DP - 2015 Aug TI - Secondary Adult Acute Myeloid Leukemia: a Review of Our Evolving Understanding of a Complex Disease Process. PG - 37 LID - 10.1007/s11864-015-0355-3 [doi] AB - OPINION STATEMENT: Secondary AML (s-AML) encompasses AML evolving from myelodysplasia (AML-MDS) and treatment-related AML (t-AML) after exposure to chemotherapy, radiation, or environmental toxins. S-AML has traditionally been considered a devastating disease, affecting a vulnerable population of heavily pretreated, older adults. A limited understanding of disease pathogenesis/heterogeneity and lack of effective treatments have hampered overall improvements in patient outcomes. With the recent understanding that the secondary nature of sAML does not by itself incur a poor prognosis and incorporation of cytogenetics and molecular genetics into patient care and the advancement of treatment, including improved supportive care, novel chemotherapeutics agents, and nonmyeloablative conditioning regimens as part of allogeneic hematopoietic cell transplantation (HCT), modest gains in survival and quality of life are beginning to be seen among patients with s-AML. FAU - Zeichner, Simon B AU - Zeichner SB AD - Department of Hematology and Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, USA, szeichn@emory.edu. FAU - Arellano, Martha L AU - Arellano ML LA - eng PT - Journal Article PT - Review PL - United States TA - Curr Treat Options Oncol JT - Current treatment options in oncology JID - 100900946 SB - IM MH - Adult MH - Humans MH - Leukemia, Myeloid, Acute/*diagnosis/epidemiology/etiology/*therapy MH - *Neoplasms, Second Primary MH - Prognosis MH - Risk EDAT- 2015/07/06 06:00 MHDA- 2016/03/25 06:00 CRDT- 2015/07/06 06:00 AID - 10.1007/s11864-015-0355-3 [doi] PST - ppublish SO - Curr Treat Options Oncol. 2015 Aug;16(8):37. doi: 10.1007/s11864-015-0355-3. PMID- 26134365 OWN - NLM STAT- MEDLINE DA - 20150908 DCOM- 20160321 IS - 1865-3774 (Electronic) IS - 0925-5710 (Linking) VI - 102 IP - 3 DP - 2015 Sep TI - Serum level of miR-10-5p as a prognostic biomarker for acute myeloid leukemia. PG - 296-303 LID - 10.1007/s12185-015-1829-6 [doi] AB - MicroRNAs (miRNAs) are a type of small non-coding RNA molecule that play important roles in tumor initiation, chemotherapy response, promotion, and progression by negatively interfering with gene expression. The aim of the present study was to investigate the serum expression status and explore the prognostic significance of miR-10a-5p in acute myeloid leukemia (AML). The serum expression level of miR-10a-5p in de novo AML was significantly higher, compared with that in controls. The area under the receiver operator characteristic (ROC) curve was of 0.831 in the diagnostic value of miR-10a-5p. In the complete remission (CR) group, the serum expression level of miR-10a-5p was similar to that of healthy subjects and demonstrated a significant downtrend when compared to that on the day of diagnosis. Nevertheless, miR-10a-5p expression was found to significantly increase in cases of relapsed AML when compared individually to the CR population. On analysis of the association of miR-10a-5p expression with the clinical characteristics at diagnosis in AML patients, lower CR rates occurred more frequently in the high-expression group. In addition, high miR-10a-5p expression was associated with poorer overall survival (OS). These data suggest that miR-10a-5p may serve as a biomarker useful to improving the management of AML patients. FAU - Zhi, Yongjin AU - Zhi Y AD - Department of Hematology, Third Affiliated Hospital of Soochow University, #185 Juqian Road, Changzhou, 213000, Jiangsu, China. FAU - Xie, Xiaobao AU - Xie X FAU - Wang, Rong AU - Wang R FAU - Wang, Biao AU - Wang B FAU - Gu, Weiying AU - Gu W FAU - Ling, Yun AU - Ling Y FAU - Dong, Weimin AU - Dong W FAU - Zhi, Feng AU - Zhi F FAU - Liu, Yan AU - Liu Y LA - eng PT - Clinical Trial PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150702 PL - Japan TA - Int J Hematol JT - International journal of hematology JID - 9111627 RN - 0 (Biomarkers, Tumor) RN - 0 (MIRN10 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (RNA, Neoplasm) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Aged, 80 and over MH - Biomarkers, Tumor/*blood MH - Disease-Free Survival MH - Female MH - *Gene Expression Regulation, Leukemic MH - Humans MH - Leukemia, Myeloid, Acute/*blood/mortality/therapy MH - Male MH - MicroRNAs/*blood MH - Middle Aged MH - RNA, Neoplasm/*blood MH - Survival Rate EDAT- 2015/07/03 06:00 MHDA- 2016/03/22 06:00 CRDT- 2015/07/03 06:00 PHST- 2014/12/29 [received] PHST- 2015/06/18 [accepted] PHST- 2015/06/11 [revised] PHST- 2015/07/02 [aheadofprint] AID - 10.1007/s12185-015-1829-6 [doi] PST - ppublish SO - Int J Hematol. 2015 Sep;102(3):296-303. doi: 10.1007/s12185-015-1829-6. Epub 2015 Jul 2. PMID- 26126642 OWN - NLM STAT- MEDLINE DA - 20150908 DCOM- 20160321 IS - 1865-3774 (Electronic) IS - 0925-5710 (Linking) VI - 102 IP - 3 DP - 2015 Sep TI - Outcome of adolescent patients with acute myeloid leukemia treated with pediatric protocols. PG - 318-26 LID - 10.1007/s12185-015-1825-x [doi] AB - As past studies of adolescent and young adults (AYA) with acute myeloid leukemia (AML) reported conflicting results, we conducted a retrospective analysis using data from three Japanese pediatric AML studies. Among the 782 patients with de novo AML, 44 were classified as AYA (age >/=15 years at diagnosis), 164 as infants (0-1 year), 413 as younger children (2-11 years), and 161 as older children (12-14 years). While the 5-year event-free survival rate of AYA was not different among the groups, the five-year survival rate (54.7 %) was significantly lower than that of the other three groups (P = 0.019): 68.7 % for infants, 73.2 % for younger children, and 75.5 % for older children. No difference in the 5-year cumulative incidence of relapse was observed, but treatment-related death (TRD) of AYA was significantly higher (29.4 %) than that in infants (14.8 %), younger children (10.2 %), and older children (13.8 %). Multivariate analysis showed age >/=15 years old at diagnosis was associated with both poor survival rate and high TRD. Adolescents with AML had inferior survival due to a higher incidence of TRD, especially after failure of initial frontline treatment. FAU - Tomizawa, Daisuke AU - Tomizawa D AD - Division of Leukemia and Lymphoma, Children's Cancer Center, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan, tomizawa-d@ncchd.go.jp. FAU - Watanabe, Tomoyuki AU - Watanabe T FAU - Hanada, Ryoji AU - Hanada R FAU - Horibe, Keizo AU - Horibe K FAU - Horikoshi, Yasuo AU - Horikoshi Y FAU - Iwamoto, Shotaro AU - Iwamoto S FAU - Kinoshita, Akitoshi AU - Kinoshita A FAU - Moritake, Hiroshi AU - Moritake H FAU - Nakayama, Hideki AU - Nakayama H FAU - Shimada, Akira AU - Shimada A FAU - Taga, Takashi AU - Taga T FAU - Takahashi, Hiroyuki AU - Takahashi H FAU - Tawa, Akio AU - Tawa A FAU - Terui, Kiminori AU - Terui K FAU - Hori, Hiroki AU - Hori H FAU - Kawano, Yoshifumi AU - Kawano Y FAU - Kikuta, Atsushi AU - Kikuta A FAU - Manabe, Atsushi AU - Manabe A FAU - Adachi, Souichi AU - Adachi S LA - eng PT - Clinical Trial PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20150701 PL - Japan TA - Int J Hematol JT - International journal of hematology JID - 9111627 SB - IM MH - Adolescent MH - Adult MH - Age Factors MH - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/adverse effects MH - Child MH - Child, Preschool MH - Disease-Free Survival MH - Female MH - Humans MH - Infant MH - Infant, Newborn MH - Leukemia, Myeloid, Acute/*drug therapy/*mortality MH - Male MH - Survival Rate EDAT- 2015/07/02 06:00 MHDA- 2016/03/22 06:00 CRDT- 2015/07/02 06:00 PHST- 2015/03/24 [received] PHST- 2015/06/18 [accepted] PHST- 2015/06/09 [revised] PHST- 2015/07/01 [aheadofprint] AID - 10.1007/s12185-015-1825-x [doi] PST - ppublish SO - Int J Hematol. 2015 Sep;102(3):318-26. doi: 10.1007/s12185-015-1825-x. Epub 2015 Jul 1. PMID- 26125711 OWN - NLM STAT- MEDLINE DA - 20150701 DCOM- 20160324 IS - 1676-5680 (Electronic) IS - 1676-5680 (Linking) VI - 14 IP - 2 DP - 2015 TI - Effects of changes in serum endostatin and fibroblast growth factor 19 on the chemotherapeutic sensitivity in acute myeloid leukemia patients. PG - 5181-7 LID - 10.4238/2015.May.18.8 [doi] AB - The present study aimed to explore the changes in serum endostatin and fibroblast growth factor 19 (FGF-19) in acute myeloid leukemia patients, and to determine their effects on chemotherapeutic sensitivity. Sixty acute myeloid leukemia patients and 30 healthy controls were included in the study. Patient serum endostatin and FGF-19 levels were measured on admission, and then, standard chemotherapy was administered. The patients were divided into 2 groups according to chemotherapeutic effects: 21 patients in the chemotherapeutic sensitivity group (complete remission + partial remission) and 39 in the chemotherapeutic resistance group (no remission + degradation). A receiver operating characteristic (ROC) curve was used to analyze the relationship of serum endostatin and FGF-19 levels with chemotherapeutic sensitivity in acute myeloid leukemia patients. The levels of serum endostatin and FGF-19 in acute myeloid leukemia patients before chemotherapy were significantly higher than those in the control group. Moreover, these levels significantly decreased after chemotherapy (P < 0.01). The levels of serum endostatin and FGF-19 in the chemotherapeutic sensitivity group were lower than those in the chemotherapeutic resistance group, both before and after chemotherapy (P < 0.05 and P < 0.01, respectively). ROC curve analysis showed that the predictive values of endostatin and FGF-19 were good, and there was no significant difference between these results. In conclusion, serum endostatin and FGF-19 can be used as predictors of chemotherapeutic sensitivity for acute myeloid leukemia patients, and may be important for determining prognosis. FAU - Su, Y Z AU - Su YZ AD - Department of Hematology, The First Affiliated Hospital of Shantou University Medical College, Shantou, China. FAU - Wang, C B AU - Wang CB AD - Department of Tumor and Hematology, Yancheng Hospital Affiliated to Southeast University (The Third People's Hospital of Yancheng), Yancheng, China chunbinwang@126.com. FAU - Zhou, Y AU - Zhou Y AD - Department of Tumor and Hematology, Yancheng Hospital Affiliated to Southeast University (The Third People's Hospital of Yancheng), Yancheng, China. FAU - Sun, N T AU - Sun NT AD - Department of Tumor and Hematology, Yancheng Hospital Affiliated to Southeast University (The Third People's Hospital of Yancheng), Yancheng, China. LA - eng PT - Journal Article DEP - 20150518 PL - Brazil TA - Genet Mol Res JT - Genetics and molecular research : GMR JID - 101169387 RN - 0 (Biomarkers, Pharmacological) RN - 0 (Endostatins) RN - 0 (FGF19 protein, human) RN - 0 (Harringtonines) RN - 04079A1RDZ (Cytarabine) RN - 62031-54-3 (Fibroblast Growth Factors) RN - 6FG8041S5B (homoharringtonine) RN - ZRP63D75JW (Idarubicin) RN - ZS7284E0ZP (Daunorubicin) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use MH - Biomarkers, Pharmacological/blood MH - Case-Control Studies MH - Cytarabine/therapeutic use MH - Daunorubicin/therapeutic use MH - Drug Resistance, Neoplasm/genetics MH - Endostatins/*blood/genetics MH - Female MH - Fibroblast Growth Factors/*blood/genetics MH - Gene Expression MH - Harringtonines/therapeutic use MH - Humans MH - Idarubicin/therapeutic use MH - Leukemia, Myeloid, Acute/*blood/drug therapy/genetics/pathology MH - Male MH - Middle Aged MH - Prognosis MH - ROC Curve MH - Remission Induction MH - Treatment Outcome EDAT- 2015/07/01 06:00 MHDA- 2016/03/25 06:00 CRDT- 2015/07/01 06:00 AID - gmr5491 [pii] AID - 10.4238/2015.May.18.8 [doi] PST - epublish SO - Genet Mol Res. 2015 May 18;14(2):5181-7. doi: 10.4238/2015.May.18.8. PMID- 26110921 OWN - NLM STAT- MEDLINE DA - 20150626 DCOM- 20160325 LR - 20150702 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 10 IP - 6 DP - 2015 TI - Tetraarsenictetrasulfide and Arsenic Trioxide Exert Synergistic Effects on Induction of Apoptosis and Differentiation in Acute Promyelocytic Leukemia Cells. PG - e0130343 LID - 10.1371/journal.pone.0130343 [doi] AB - Since arsenic trioxide (As3+) has been successfully used in the treatment of acute promyelocytic leukemia (APL), its adverse effects on patients have been problematic and required a solution. Considering the good therapeutic potency and low toxicity of tetraarsenictetrasulfide (As4S4) in the treatment of APL, we investigated the effects of combining As4S4 and As3+ on the apoptosis and differentiation of NB4 and primary APL cells. As4S4, acting similarly to As3+, arrested the G1/S transition, induced the accumulation of cellular reactive oxygen species, and promoted apoptosis. Additionally, low concentrations of As4S4 (0.1-0.4 muM) induced differentiation of NB4 and primary APL cells. Compared with the As4S4- or As3+-treated groups, the combination of As4S4 and As3+ obviously promoted apoptosis and differentiation of NB4 and primary APL cells. Mechanistic studies suggested that As4S4 acted synergistically with As3+ to down-regulate Bcl-2 and nuclear factor-kappaB expression, up-regulate Bax and p53 expression, and induce activation of caspase-12 and caspase-3. Moreover, the combination of low concentrations of As4S4 and As3+ enhanced degradation of the promyelocytic leukemia-retinoic acid receptor alpha oncoprotein. In summary, As4S4 and As3+ synergistically induce the apoptosis and differentiation of NB4 and primary APL cells. FAU - Wang, Shuping AU - Wang S AD - State key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing, 210093, China. FAU - Zhou, Min AU - Zhou M AD - Department of Hematology, DrumTower Hospital of Medical School, Nanjing University, Nanjing, 210093, China. FAU - Ouyang, Jian AU - Ouyang J AD - Department of Hematology, DrumTower Hospital of Medical School, Nanjing University, Nanjing, 210093, China. FAU - Geng, Zhirong AU - Geng Z AD - State key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing, 210093, China. FAU - Wang, Zhilin AU - Wang Z AD - State key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing, 210093, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150625 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Arsenicals) RN - 0 (Neoplasm Proteins) RN - 0 (Oxides) RN - 0 (Reactive Oxygen Species) RN - 0 (Sulfides) RN - 0 (tetraarsenic tetrasulfide) RN - S7V92P67HO (arsenic trioxide) SB - IM MH - Apoptosis/drug effects MH - Arsenicals/*administration & dosage MH - Cell Differentiation/drug effects MH - Drug Resistance, Neoplasm MH - *Drug Synergism MH - Gene Expression Regulation, Neoplastic/drug effects MH - Humans MH - Leukemia, Promyelocytic, Acute/*drug therapy/genetics/pathology MH - Neoplasm Proteins/biosynthesis/genetics MH - Oxides/*administration & dosage MH - Reactive Oxygen Species/metabolism MH - Sulfides/*administration & dosage PMC - PMC4481354 OID - NLM: PMC4481354 EDAT- 2015/06/26 06:00 MHDA- 2016/03/26 06:00 CRDT- 2015/06/26 06:00 PHST- 2015 [ecollection] PHST- 2015/01/21 [received] PHST- 2015/05/19 [accepted] PHST- 2015/06/25 [epublish] AID - 10.1371/journal.pone.0130343 [doi] AID - PONE-D-14-57601 [pii] PST - epublish SO - PLoS One. 2015 Jun 25;10(6):e0130343. doi: 10.1371/journal.pone.0130343. eCollection 2015. PMID- 26107207 OWN - NLM STAT- MEDLINE DA - 20150625 DCOM- 20160322 IS - 1513-7368 (Print) IS - 1513-7368 (Linking) VI - 16 IP - 11 DP - 2015 TI - Prognostic Value of a CYP2B6 Gene Polymorphism in Patients with Acute Myeloid Leukemia. PG - 4583-7 AB - BACKGROUND: The objectives of this study aimed to detect a CYP2B6 polymorphism in de novo cases of acute myeloid leukemia patients and identify any role in disease progression and outcome. MATERIALS AND METHODS: DNA was isolated from peripheral blood of 82 newly diagnosed acute myeloid leukemia cases and the CYP2B6 G15631T gene polymorphism was assayed by PCR restriction fragment length polymorphism (PCR-RFLP). RESULTS: The frequency of the GG genotype (wild type) was 48 (58.5%) and that of the mutant type T allele was 34 (41.9%). GT genotype heterozygous variants were found in 28 (34%), and TT genotype homozygous variants in 6 (7.3%) cases. We found no significant association between the CYP2B6 G15631T polymorphism and complete response (CR) (p-value=0.768), FAB classification (p-value=0.51), cytogenetic analysis (p-value=0.673), and overall survival (p-value=0.325). Also, there were no significant links with early toxic death (p-value=0.92) or progression- free survival (PFS) (p-value=0.245). CONCLUSIONS: Our results suggest that the CYP2B6 polymorphism has no role in disease progression, therapeutic outcome, patient free survival, early toxic death and overall survival in acute myeloid leukemia patients. FAU - Alazhary, Nevin M AU - Alazhary NM AD - Department of Clinical Pathology, National Cancer Institute, Cairo University, Cairo, Egypt E-mail : nevin_elazhary@hotmail.com. FAU - Shafik, Roxan E AU - Shafik RE FAU - Shafik, Hanan E AU - Shafik HE FAU - Kamel, Mahmoud M AU - Kamel MM LA - eng PT - Journal Article PL - Thailand TA - Asian Pac J Cancer Prev JT - Asian Pacific journal of cancer prevention : APJCP JID - 101130625 RN - 0 (Biomarkers, Tumor) RN - EC 1.14.14.1 (Cytochrome P-450 CYP2B6) SB - IM MH - Adult MH - Biomarkers, Tumor/*genetics MH - Cytochrome P-450 CYP2B6/*genetics MH - Cytogenetic Analysis MH - Female MH - Follow-Up Studies MH - Gene Frequency MH - Genotype MH - Humans MH - Leukemia, Myeloid, Acute/*genetics/*mortality/pathology MH - Male MH - Neoplasm Staging MH - Polymerase Chain Reaction MH - Polymorphism, Restriction Fragment Length MH - Polymorphism, Single Nucleotide/*genetics MH - Prognosis MH - Remission Induction MH - Survival Rate EDAT- 2015/06/25 06:00 MHDA- 2016/03/24 06:00 CRDT- 2015/06/25 06:00 PST - ppublish SO - Asian Pac J Cancer Prev. 2015;16(11):4583-7. PMID- 26045745 OWN - NLM STAT- MEDLINE DA - 20150605 DCOM- 20160308 LR - 20150607 IS - 1936-2625 (Electronic) IS - 1936-2625 (Linking) VI - 8 IP - 3 DP - 2015 TI - Down-regulation of GPX3 is associated with favorable/intermediate karyotypes in de novo acute myeloid leukemia. PG - 2384-91 AB - Decreased glutathione peroxidase 3 (GPX3) expression has been identified in numerous solid tumors. However, GPX3 expression pattern in acute myeloid leukemia (AML) remains poorly known. Our study was intended to explore GPX3 expression status and further analyze the clinical relevance of GPX3 expression in AML. GPX3 mRNA level was detected by real-time quantitative PCR in 122 de novo AML patients and 44 normal controls. GPX3 transcript level was significantly decreased compared with normal controls (P<0.001). The patients with low GPX3 expression had significantly higher hemoglobin and platelets than those with high GPX3 expression (P=0.049 and 0.020). The frequency of low GPX3 expression in favorable karyotype (66%, 23/35) and intermediate karyotype (65%, 45/69) was higher than in poor karyotype (29%, 4/14) (P=0.017). No significant differences were observed in both complete remission and overall survival between the GPX3 low-expressed and high-expressed patients (P>0.05). Reduced GPX3 expression is associated with favorable/intermediate karyotypes but not with survival in de novo AML patients. FAU - Zhou, Jing-Dong AU - Zhou JD AD - Department of Hematology, Affiliated People's Hospital of Jiangsu University Zhenjiang, Jiangsu, People's Republic of China. FAU - Wen, Xiang-Mei AU - Wen XM AD - Laboratory Center, Affiliated People's Hospital of Jiangsu University Zhenjiang, Jiangsu, People's Republic of China. FAU - Zhang, Ying-Ying AU - Zhang YY AD - Department of Hematology, Affiliated People's Hospital of Jiangsu University Zhenjiang, Jiangsu, People's Republic of China. FAU - Yang, Lei AU - Yang L AD - Department of Hematology, Affiliated People's Hospital of Jiangsu University Zhenjiang, Jiangsu, People's Republic of China. FAU - Ma, Yu-Juan AU - Ma YJ AD - Department of Hematology, Affiliated People's Hospital of Jiangsu University Zhenjiang, Jiangsu, People's Republic of China. FAU - Ma, Ji-Chun AU - Ma JC AD - Laboratory Center, Affiliated People's Hospital of Jiangsu University Zhenjiang, Jiangsu, People's Republic of China. FAU - Yang, Jing AU - Yang J AD - Department of Hematology, Affiliated People's Hospital of Jiangsu University Zhenjiang, Jiangsu, People's Republic of China. FAU - Guo, Hong AU - Guo H AD - Laboratory Center, Affiliated People's Hospital of Jiangsu University Zhenjiang, Jiangsu, People's Republic of China. FAU - Yao, Dong-Ming AU - Yao DM AD - Laboratory Center, Affiliated People's Hospital of Jiangsu University Zhenjiang, Jiangsu, People's Republic of China. FAU - Lin, Jiang AU - Lin J AD - Laboratory Center, Affiliated People's Hospital of Jiangsu University Zhenjiang, Jiangsu, People's Republic of China. FAU - Qian, Jun AU - Qian J AD - Department of Hematology, Affiliated People's Hospital of Jiangsu University Zhenjiang, Jiangsu, People's Republic of China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150301 PL - United States TA - Int J Clin Exp Pathol JT - International journal of clinical and experimental pathology JID - 101480565 RN - 0 (Biomarkers, Tumor) RN - 0 (Hemoglobins) RN - 0 (RNA, Messenger) RN - EC 1.11.1.- (GPX3 protein, human) RN - EC 1.11.1.9 (Glutathione Peroxidase) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Aged, 80 and over MH - Biomarkers, Tumor/*genetics/metabolism MH - Case-Control Studies MH - Child MH - Down-Regulation MH - Female MH - Genetic Predisposition to Disease MH - Glutathione Peroxidase/*genetics/metabolism MH - Hemoglobins/analysis MH - Humans MH - K562 Cells MH - Kaplan-Meier Estimate MH - *Karyotype MH - Karyotyping MH - Leukemia, Myeloid, Acute/blood/enzymology/*genetics/mortality MH - Male MH - Middle Aged MH - Phenotype MH - Platelet Count MH - Predictive Value of Tests MH - Prognosis MH - RNA, Messenger/genetics MH - Real-Time Polymerase Chain Reaction MH - Risk Factors MH - Time Factors MH - Young Adult PMC - PMC4440054 OID - NLM: PMC4440054 OTO - NOTNLM OT - GPX3 OT - acute myeliod leukemia OT - expression OT - karyotype EDAT- 2015/06/06 06:00 MHDA- 2016/03/10 06:00 CRDT- 2015/06/06 06:00 PHST- 2015 [ecollection] PHST- 2015/01/07 [received] PHST- 2015/02/27 [accepted] PHST- 2015/03/01 [epublish] PST - epublish SO - Int J Clin Exp Pathol. 2015 Mar 1;8(3):2384-91. eCollection 2015. PMID- 26045292 OWN - NLM STAT- MEDLINE DA - 20150905 DCOM- 20160321 LR - 20160324 IS - 1592-8721 (Electronic) IS - 0390-6078 (Linking) VI - 100 IP - 9 DP - 2015 Sep TI - Adverse prognostic effect of homozygous TET2 mutation on the relapse risk of acute myeloid leukemia in patients of normal karyotype. PG - e351-3 LID - 10.3324/haematol.2015.126227 [doi] FAU - Ahn, Jae-Sook AU - Ahn JS AD - Hematology-Oncology, Chonnam National University Hwasun Hospital, Jeollanam-do, Republic of Korea. FAU - Kim, Hyeoung-Joon AU - Kim HJ AD - Hematology-Oncology, Chonnam National University Hwasun Hospital, Jeollanam-do, Republic of Korea hjoonk@chonnam.ac.kr. FAU - Kim, Yeo-Kyeoung AU - Kim YK AD - Hematology-Oncology, Chonnam National University Hwasun Hospital, Jeollanam-do, Republic of Korea. FAU - Jung, Sung-Hoon AU - Jung SH AD - Hematology-Oncology, Chonnam National University Hwasun Hospital, Jeollanam-do, Republic of Korea. FAU - Yang, Deok-Hwan AU - Yang DH AD - Hematology-Oncology, Chonnam National University Hwasun Hospital, Jeollanam-do, Republic of Korea. FAU - Lee, Je-Jung AU - Lee JJ AD - Hematology-Oncology, Chonnam National University Hwasun Hospital, Jeollanam-do, Republic of Korea. FAU - Lee, Il-Kwon AU - Lee IK AD - Genomic Research Center for Hematopoietic Diseases, Chonnam National University Hwasun Hospital, Jeollanam-do, Republic of Korea. FAU - Kim, Nan Young AU - Kim NY AD - Genomic Research Center for Hematopoietic Diseases, Chonnam National University Hwasun Hospital, Jeollanam-do, Republic of Korea. FAU - Minden, Mark D AU - Minden MD AD - Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Canada. FAU - Jung, Chul Won AU - Jung CW AD - Division of Hematology-Oncology, Samsung Medical Center, Seoul, Republic of Korea. FAU - Jang, Jun-Ho AU - Jang JH AD - Division of Hematology-Oncology, Samsung Medical Center, Seoul, Republic of Korea. FAU - Kim, Hee Je AU - Kim HJ AD - Department of Hematology, The Catholic University of Korea, Seoul, Republic of Korea. FAU - Moon, Joon Ho AU - Moon JH AD - Department of Hematology-Oncology, Kyungpook National University Hospital, Daegu, Republic of Korea. FAU - Sohn, Sang Kyun AU - Sohn SK AD - Department of Hematology-Oncology, Kyungpook National University Hospital, Daegu, Republic of Korea. FAU - Won, Jong-Ho AU - Won JH AD - Department of Hematology-Oncology, Soon Chun Hyang University Hospital, Seoul, Republic of Korea. FAU - Kim, Sung-Hyun AU - Kim SH AD - Department of Hematology-Oncology, Dong-A University College of Medicine, Busan, Republic of Korea. FAU - Kim, Namshin AU - Kim N AD - Epigenomics Research Center, Genome Institute, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea. FAU - Yoshida, Kenichi AU - Yoshida K AD - Kyoto University, Japan. FAU - Ogawa, Seishi AU - Ogawa S AD - Kyoto University, Japan. FAU - Kim, Dennis Dong Hwan AU - Kim DD AD - Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Canada. LA - eng PT - Evaluation Studies PT - Letter PT - Research Support, Non-U.S. Gov't DEP - 20150604 PL - Italy TA - Haematologica JT - Haematologica JID - 0417435 RN - 0 (DNA-Binding Proteins) RN - 0 (Proto-Oncogene Proteins) RN - 0 (TET2 protein, human) SB - IM MH - Adolescent MH - Adult MH - DNA-Binding Proteins/*genetics MH - Disease-Free Survival MH - Female MH - Follow-Up Studies MH - *Homozygote MH - Humans MH - *Karyotype MH - *Leukemia, Myeloid, Acute/drug therapy/genetics/mortality MH - Male MH - Middle Aged MH - *Mutation MH - Proto-Oncogene Proteins/*genetics MH - Survival Rate PMC - PMC4800711 OID - NLM: PMC4800711 OTO - NOTNLM OT - TET2 OT - acute myeloid leukemia OT - homozygous mutation OT - normal karyotype EDAT- 2015/06/06 06:00 MHDA- 2016/03/22 06:00 CRDT- 2015/06/06 06:00 PHST- 2015/06/04 [aheadofprint] AID - haematol.2015.126227 [pii] AID - 10.3324/haematol.2015.126227 [doi] PST - ppublish SO - Haematologica. 2015 Sep;100(9):e351-3. doi: 10.3324/haematol.2015.126227. Epub 2015 Jun 4. PMID- 26043219 OWN - NLM STAT- MEDLINE DA - 20150605 DCOM- 20160229 IS - 1744-8301 (Electronic) IS - 1479-6694 (Linking) VI - 11 IP - 11 DP - 2015 TI - 3q26/EVI1 rearrangements in myeloid hemopathies: a cytogenetic review. PG - 1675-86 LID - 10.2217/fon.15.64 [doi] AB - The EVI1 gene, located in chromosomal band 3q26, is a transcription factor that has stem cell-specific expression pattern and is essential for the regulation of self-renewal of hematopoietic stem cells. It is now recognized as one of the dominant oncogenes associated with myeloid leukemia. EVI1 overexpression is associated with minimal to no response to chemotherapy and poor clinical outcome. Several chromosomal rearrangements involving band 3q26 are known to induce EVI1 overexpression. They are mainly found in acute myeloid leukemia and blastic phase of Philadelphia chromosome-positive chronic myeloid leukemia, more rarely in myelodysplastic syndromes. They include inv(3)(q21q26), t(3;3)(q21;q26), t(3;21)(q26;q22), t(3;12)(q26;p13) and t(2;3)(p15-23;q26). However, many other chromosomal rearrangements involving 3q26/EVI1 have been identified. The precise molecular event has not been elucidated in the majority of these chromosomal abnormalities and most gene partners remain unknown. FAU - De Braekeleer, Marc AU - De Braekeleer M AD - 1Laboratoire d'Histologie, Embryologie et Cytogenetique, Faculte de Medecine et des Sciences de la Sante, Universite de Brest, Brest, France. AD - 2Institut National de la Sante et de la Recherche Medicale (INSERM), U1078, Brest, France. AD - 3Service de Cytogenetique et Biologie de la Reproduction, Hopital Morvan, CHRU Brest, Brest, France. FAU - Le Bris, Marie-Josee AU - Le Bris MJ AD - 3Service de Cytogenetique et Biologie de la Reproduction, Hopital Morvan, CHRU Brest, Brest, France. FAU - De Braekeleer, Etienne AU - De Braekeleer E AD - 5Haematological Cancer Genetics, Wellcome Trust Sanger Institute, Cambridge, UK. FAU - Basinko, Audrey AU - Basinko A AD - 2Institut National de la Sante et de la Recherche Medicale (INSERM), U1078, Brest, France. AD - 3Service de Cytogenetique et Biologie de la Reproduction, Hopital Morvan, CHRU Brest, Brest, France. FAU - Morel, Frederic AU - Morel F AD - 1Laboratoire d'Histologie, Embryologie et Cytogenetique, Faculte de Medecine et des Sciences de la Sante, Universite de Brest, Brest, France. AD - 2Institut National de la Sante et de la Recherche Medicale (INSERM), U1078, Brest, France. AD - 3Service de Cytogenetique et Biologie de la Reproduction, Hopital Morvan, CHRU Brest, Brest, France. FAU - Douet-Guilbert, Nathalie AU - Douet-Guilbert N AD - 1Laboratoire d'Histologie, Embryologie et Cytogenetique, Faculte de Medecine et des Sciences de la Sante, Universite de Brest, Brest, France. AD - 2Institut National de la Sante et de la Recherche Medicale (INSERM), U1078, Brest, France. AD - 3Service de Cytogenetique et Biologie de la Reproduction, Hopital Morvan, CHRU Brest, Brest, France. LA - eng PT - Journal Article PT - Review PL - England TA - Future Oncol JT - Future oncology (London, England) JID - 101256629 RN - 0 (DNA-Binding Proteins) RN - 0 (MECOM protein, human) RN - 0 (Transcription Factors) SB - IM MH - Chromosome Breakpoints MH - Chromosomes, Human, Pair 3 MH - DNA-Binding Proteins/*genetics MH - Gene Expression MH - *Gene Rearrangement MH - Humans MH - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*genetics MH - Leukemia, Myeloid, Acute/*genetics MH - Proto-Oncogenes/*genetics MH - Transcription Factors/*genetics OTO - NOTNLM OT - EVI1 OT - breakpoint distribution OT - chromosomal abnormalities OT - chromosome 3 OT - myeloid hemopathies EDAT- 2015/06/05 06:00 MHDA- 2016/03/02 06:00 CRDT- 2015/06/05 06:00 AID - 10.2217/fon.15.64 [doi] PST - ppublish SO - Future Oncol. 2015;11(11):1675-86. doi: 10.2217/fon.15.64. PMID- 26022709 OWN - NLM STAT- MEDLINE DA - 20150905 DCOM- 20160321 LR - 20160324 IS - 1592-8721 (Electronic) IS - 0390-6078 (Linking) VI - 100 IP - 9 DP - 2015 Sep TI - Randomized multicenter phase II study of flavopiridol (alvocidib), cytarabine, and mitoxantrone (FLAM) versus cytarabine/daunorubicin (7+3) in newly diagnosed acute myeloid leukemia. PG - 1172-9 LID - 10.3324/haematol.2015.125849 [doi] AB - Serial studies have demonstrated that induction therapy with FLAM [flavopiridol (alvocidib) 50 mg/m(2) days 1-3, cytarabine 667 mg/m(2)/day continuous infusion days 6-8, and mitoxantrone (FLAM) 40 mg/m(2) day 9] yields complete remission rates of nearly 70% in newly diagnosed poor-risk acute myeloid leukemia. Between May 2011-July 2013, 165 newly diagnosed acute myeloid leukemia patients (age 18-70 years) with intermediate/adverse-risk cytogenetics were randomized 2:1 to receive FLAM or 7+3 (cytarabine 100 mg/m(2)/day continuous infusion days 1-7 and daunorubicin 90 mg/m(2) days 1-3), across 10 institutions. Some patients on 7+3 with residual leukemia on day 14 received 5+2 (cytarabine 100 mg/m(2)/day continuous infusion days 1-5 and daunorubicin 45 mg/m(2) days 1-2), whereas patients on FLAM were not re-treated based on day 14 bone marrow findings. The primary objective was to compare complete remission rates between one cycle of FLAM and one cycle of 7+3. Secondary end points included safety, overall survival and event-free survival. FLAM led to higher complete remission rates than 7+3 alone (70% vs. 46%; P=0.003) without an increase in toxicity, and this improvement persisted after 7+3+/-5+2 (70% vs. 57%; P=0.08). There were no significant differences in overall survival and event-free survival in both arms but post-induction strategies were not standardized. These results substantiate the efficacy of FLAM induction in newly diagnosed AML. A phase III study is currently in development. This study is registered with clinicaltrials.gov identifier: 01349972. CI - Copyright(c) Ferrata Storti Foundation. FAU - Zeidner, Joshua F AU - Zeidner JF AD - The Johns Hopkins Hospital, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA University of North Carolina, Lineberger Comprehensive Cancer Center, Chapel Hill, NC, USA joshua_zeidner@med.unc.edu. FAU - Foster, Matthew C AU - Foster MC AD - University of North Carolina, Lineberger Comprehensive Cancer Center, Chapel Hill, NC, USA. FAU - Blackford, Amanda L AU - Blackford AL AD - The Johns Hopkins Hospital, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA. FAU - Litzow, Mark R AU - Litzow MR AD - Mayo Clinic, Rochester, MN, USA. FAU - Morris, Lawrence E AU - Morris LE AD - The Blood and Marrow Transplant Program at Northside Hospital, Bone Marrow Transplant Group of Georgia, Atlanta, GA, USA. FAU - Strickland, Stephen A AU - Strickland SA AD - Vanderbilt-Ingram Cancer Center, Nashville, TN, USA. FAU - Lancet, Jeffrey E AU - Lancet JE AD - H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. FAU - Bose, Prithviraj AU - Bose P AD - Virginia Commonwealth University, Massey Cancer Center, Richmond, VA, USA. FAU - Levy, M Yair AU - Levy MY AD - Texas Oncology, Baylor Charles A. Simmons Cancer Center, Dallas, TX, USA. FAU - Tibes, Raoul AU - Tibes R AD - Mayo Clinic, Scottsdale, AZ, USA. FAU - Gojo, Ivana AU - Gojo I AD - The Johns Hopkins Hospital, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA University of Maryland Medical Center, Stewart Greenebaum Cancer Center, Baltimore, MD, USA. FAU - Gocke, Christopher D AU - Gocke CD AD - The Johns Hopkins Hospital, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA. FAU - Rosner, Gary L AU - Rosner GL AD - The Johns Hopkins Hospital, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA. FAU - Little, Richard F AU - Little RF AD - National Cancer Institute, Rockville, MD, USA. FAU - Wright, John J AU - Wright JJ AD - National Cancer Institute, Rockville, MD, USA. FAU - Doyle, L Austin AU - Doyle LA AD - National Cancer Institute, Rockville, MD, USA. FAU - Smith, B Douglas AU - Smith BD AD - The Johns Hopkins Hospital, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA. FAU - Karp, Judith E AU - Karp JE AD - The Johns Hopkins Hospital, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA. LA - eng SI - ClinicalTrials.gov/NCT01349972 GR - 2P30 CA06973-46/CA/NCI NIH HHS/United States GR - P30 CA006973/CA/NCI NIH HHS/United States GR - U01 CA70095/CA/NCI NIH HHS/United States GR - UL1 TR001079/TR/NCATS NIH HHS/United States GR - UM1 CA186691/CA/NCI NIH HHS/United States PT - Clinical Trial, Phase II PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, N.I.H., Extramural DEP - 20150528 PL - Italy TA - Haematologica JT - Haematologica JID - 0417435 RN - 0 (Flavonoids) RN - 0 (Piperidines) RN - 04079A1RDZ (Cytarabine) RN - 45AD6X575G (alvocidib) RN - BZ114NVM5P (Mitoxantrone) RN - ZS7284E0ZP (Daunorubicin) SB - IM CIN - Haematologica. 2015 Sep;100(9):1105-7. PMID: 26341523 MH - Adult MH - Aged MH - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/adverse effects MH - Cytarabine/administration & dosage/adverse effects MH - Daunorubicin/administration & dosage/adverse effects MH - Disease-Free Survival MH - Female MH - Flavonoids/administration & dosage/adverse effects MH - Follow-Up Studies MH - Humans MH - *Leukemia, Myeloid, Acute/diagnosis/drug therapy/mortality MH - Male MH - Middle Aged MH - Mitoxantrone/administration & dosage/adverse effects MH - Piperidines/administration & dosage/adverse effects MH - Survival Rate PMC - PMC4800702 OID - NLM: PMC4800702 EDAT- 2015/05/30 06:00 MHDA- 2016/03/22 06:00 CRDT- 2015/05/30 06:00 PHST- 2015/02/16 [received] PHST- 2015/05/21 [accepted] PHST- 2015/05/28 [aheadofprint] AID - haematol.2015.125849 [pii] AID - 10.3324/haematol.2015.125849 [doi] PST - ppublish SO - Haematologica. 2015 Sep;100(9):1172-9. doi: 10.3324/haematol.2015.125849. Epub 2015 May 28. PMID- 25996682 OWN - NLM STAT- MEDLINE DA - 20150606 DCOM- 20160308 LR - 20151113 IS - 1559-2308 (Electronic) IS - 1559-2294 (Linking) VI - 10 IP - 6 DP - 2015 TI - Identification of differentially methylated markers among cytogenetic risk groups of acute myeloid leukemia. PG - 526-35 LID - 10.1080/15592294.2015.1048060 [doi] AB - Aberrant DNA methylation is known to occur in cancer, including hematological malignancies such as acute myeloid leukemia (AML). However, less is known about whether specific methylation profiles characterize specific subcategories of AML. We examined this issue by using comprehensive high-throughput array-based relative methylation analysis (CHARM) to compare methylation profiles among patients in different AML cytogenetic risk groups. We found distinct profiles in each group, with the high-risk group showing overall increased methylation compared with low- and mid-risk groups. The differentially methylated regions (DMRs) distinguishing cytogenetic risk groups of AML were enriched in the CpG island shores. Specific risk-group associated DMRs were located near genes previously known to play a role in AML or other malignancies, such as MN1, UHRF1, HOXB3, and HOXB4, as well as TRIM71, the function of which in cancer is not well characterized. These findings were verified by quantitative bisulfite pyrosequencing and by comparison with results available at the TCGA cancer genome browser. To explore the potential biological significance of the observed methylation changes, we correlated our findings with gene expression data available through the TCGA database. The results showed that decreased methylation at HOXB3 and HOXB4 was associated with increased gene expression of both HOXB genes specific to the mid-risk AML, while increased DNA methylation at DCC distinctive to the high-risk AML was associated with increased gene expression. Our results suggest that the differential impact of cytogenetic changes on AML prognosis may, in part, be mediated by changes in methylation. FAU - Qu, Xiaoyu AU - Qu X AD - a Fred Hutchinson Cancer Research Center ; Seattle , WA , USA. FAU - Davison, Jerry AU - Davison J FAU - Du, Liping AU - Du L FAU - Storer, Barry AU - Storer B FAU - Stirewalt, Derek L AU - Stirewalt DL FAU - Heimfeld, Shelly AU - Heimfeld S FAU - Estey, Elihu AU - Estey E FAU - Appelbaum, Frederick R AU - Appelbaum FR FAU - Fang, Min AU - Fang M LA - eng GR - CA018029/CA/NCI NIH HHS/United States GR - DK056465/DK/NIDDK NIH HHS/United States GR - P30 CA015704/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - Epigenetics JT - Epigenetics JID - 101265293 RN - 0 (HOXB4 protein, human) RN - 0 (Homeodomain Proteins) RN - 0 (HoxB3 protein, human) RN - 0 (Transcription Factors) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Bone Marrow/pathology MH - CpG Islands/genetics MH - DNA Methylation/*genetics MH - *Epigenesis, Genetic MH - Female MH - Gene Expression Regulation, Neoplastic MH - Homeodomain Proteins/biosynthesis/*genetics MH - Humans MH - Leukemia, Myeloid, Acute/*genetics/pathology MH - Male MH - Middle Aged MH - Promoter Regions, Genetic MH - Transcription Factors/biosynthesis/*genetics PMC - PMC4623036 OID - NLM: PMC4623036 [Available on 05/21/16] OTO - NOTNLM OT - AML OT - AML, acute myeloid leukemia OT - CHARM OT - CHARM, comprehensive high-throughput array-based relative methylation analysis OT - DMR OT - DMR, differentially methylated region OT - TCGA, The Cancer Genome Atlas Research Network OT - expression OT - methylation EDAT- 2015/05/23 06:00 MHDA- 2016/03/10 06:00 CRDT- 2015/05/22 06:00 PMCR- 2016/05/21 00:00 AID - 10.1080/15592294.2015.1048060 [doi] PST - ppublish SO - Epigenetics. 2015;10(6):526-35. doi: 10.1080/15592294.2015.1048060. PMID- 25977190 OWN - NLM STAT- MEDLINE DA - 20150515 DCOM- 20160307 LR - 20151102 IS - 1944-7930 (Electronic) IS - 1539-6509 (Linking) VI - 19 IP - 105 DP - 2015 Apr TI - New approaches for the immunotherapy of acute myeloid leukemia. PG - 275-84 AB - Acute myeloid leukemia (AML) is a set of related diseases characterized by the immortalization and uncontrolled expansion of myeloid precursor cells. Core therapy for AML has remained unchanged for nearly 30 years, and survival rates remain unsatisfactory. However, advances in the immunotherapy of AML have created opportunities for improved outcomes. Enforcing a tumor-specific immune response through the re-direction of the adaptive immune system, which links remarkable specificity with potent cytotoxic effector functions, has proven particularly compelling. This may be coupled with immune checkpoint blockade and conventional therapies for optimal effect. Engineered antibodies are currently in use in AML and the repertoire of available therapeutics will expand. NK cells have shown effectiveness in this disease. New methods to optimize their activation and the targeting of AML show potential. Most significantly, adoptive immunotherapy with tumor-specific T cells, and particularly T cells re-directed using genetically introduced TCR or chimeric antigen receptors, have demonstrated promise. Each of these approaches has unique benefits and challenges that we explore in this review. FAU - Geiger, Terrence L AU - Geiger TL AD - Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. FAU - Rubnitz, Jeffrey E AU - Rubnitz JE AD - Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. LA - eng GR - P30 CA021765/CA/NCI NIH HHS/United States GR - P30-CA021765/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Review PL - United States TA - Discov Med JT - Discovery medicine JID - 101250006 RN - 0 (Antibodies) RN - 0 (Antigens) RN - 0 (Antineoplastic Agents) RN - 0 (Receptors, Antigen) SB - IM MH - Antibodies/immunology MH - Antigens/immunology MH - Antineoplastic Agents/administration & dosage MH - Graft vs Leukemia Effect MH - Humans MH - Immunotherapy, Adoptive/*methods MH - Killer Cells, Natural/immunology MH - Leukemia, Myeloid, Acute/*immunology/*therapy MH - Receptors, Antigen/chemistry MH - T-Lymphocytes/immunology MH - Treatment Outcome PMC - PMC4628787 MID - NIHMS729811 OID - NLM: NIHMS729811 [Available on 04/01/16] OID - NLM: PMC4628787 [Available on 04/01/16] EDAT- 2015/05/16 06:00 MHDA- 2016/03/08 06:00 CRDT- 2015/05/16 06:00 PMCR- 2016/04/01 00:00 PST - ppublish SO - Discov Med. 2015 Apr;19(105):275-84. PMID- 25960253 OWN - NLM STAT- MEDLINE DA - 20150608 DCOM- 20160308 IS - 1879-0720 (Electronic) IS - 0928-0987 (Linking) VI - 76 DP - 2015 Aug 30 TI - Inhibition of DNA topoisomerases I and II and growth inhibition of HL-60 cells by novel acridine-based compounds. PG - 192-202 LID - 10.1016/j.ejps.2015.04.023 [doi] LID - S0928-0987(15)00178-5 [pii] AB - HL-60 cancer cells were treated with a series of novel acridine derivatives (derivatives 1-4) in order to test the compounds' ability to inhibit both cancer cell growth and topoisomerase I and II activity. Binding studies of derivatives 1-4 with calf thymus DNA were also performed using a number of techniques (UV-Vis and fluorescence spectroscopy, thermal denaturation, linear dichroism and viscometry) to determine the nature of the interaction between the compounds and ctDNA. The binding constants for the complexes of the studied acridine derivatives with DNA were calculated from UV-Vis spectroscopic titrations (K=3.1x10(4)-2.0x10(3)M(-1)). Some of the compounds showed a strong inhibitory effect against Topo II at the relatively low concentration of 5muM. Topo I/II inhibition mode assays were also performed and verified that the novel compounds are topoisomerase suppressors rather than poisons. The biological activities of derivatives were studied using MTT assay and flow cytometric methods (detection of mitochondrial membrane potential, measurement of cell viability) after 24 and 48h incubation. The ability of derivatives to impair cell proliferation was tested by an analysis of cell cycle distribution. CI - Copyright (c) 2015 Elsevier B.V. All rights reserved. FAU - Janockova, Jana AU - Janockova J AD - Department of Biochemistry, Faculty of Science, P. J. Safarik University in Kosice, Moyzesova 11, 040 01 Kosice, Slovak Republic. FAU - Plsikova, Jana AU - Plsikova J AD - Department of Biochemistry, Faculty of Science, P. J. Safarik University in Kosice, Moyzesova 11, 040 01 Kosice, Slovak Republic. FAU - Kasparkova, Jana AU - Kasparkova J AD - Department of Biophysics, Faculty of Science, Palacky University in Olomouc, Slechtitelu 11, 78371 Olomouc, Czech Republic. FAU - Brabec, Viktor AU - Brabec V AD - Department of Biophysics, Faculty of Science, Palacky University in Olomouc, Slechtitelu 11, 78371 Olomouc, Czech Republic. FAU - Jendzelovsky, Rastislav AU - Jendzelovsky R AD - Department of Cellular Biology, Institute of Biology and Ecology, Faculty of Science, P. J. Safarik University in Kosice, Moyzesova 11, 040 01 Kosice, Slovak Republic. FAU - Mikes, Jaromir AU - Mikes J AD - Department of Cellular Biology, Institute of Biology and Ecology, Faculty of Science, P. J. Safarik University in Kosice, Moyzesova 11, 040 01 Kosice, Slovak Republic. FAU - Koval, Jan AU - Koval J AD - Department of Cellular Biology, Institute of Biology and Ecology, Faculty of Science, P. J. Safarik University in Kosice, Moyzesova 11, 040 01 Kosice, Slovak Republic. FAU - Hamulakova, Slavka AU - Hamulakova S AD - Department of Organic Chemistry, Institute of Chemistry, Faculty of Science, P. J. Safarik University in Kosice, Moyzesova 11, 040 01 Kosice, Slovak Republic. FAU - Fedorocko, Peter AU - Fedorocko P AD - Department of Cellular Biology, Institute of Biology and Ecology, Faculty of Science, P. J. Safarik University in Kosice, Moyzesova 11, 040 01 Kosice, Slovak Republic. FAU - Kuca, Kamil AU - Kuca K AD - Biomedical Research Center, University Hospital Hradec Kralove, Sokolovska 581, Hradec Kralove, Czech Republic. FAU - Kozurkova, Maria AU - Kozurkova M AD - Department of Biochemistry, Faculty of Science, P. J. Safarik University in Kosice, Moyzesova 11, 040 01 Kosice, Slovak Republic; Biomedical Research Center, University Hospital Hradec Kralove, Sokolovska 581, Hradec Kralove, Czech Republic. Electronic address: maria.kozurkova@upjs.sk. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150508 PL - Netherlands TA - Eur J Pharm Sci JT - European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences JID - 9317982 RN - 0 (Acridines) RN - 0 (Topoisomerase I Inhibitors) RN - 0 (Topoisomerase II Inhibitors) RN - 9007-49-2 (DNA) RN - 91080-16-9 (calf thymus DNA) RN - EC 5.99.1.2 (DNA Topoisomerases, Type I) RN - EC 5.99.1.2 (TOP1 protein, human) RN - EC 5.99.1.3 (DNA Topoisomerases, Type II) SB - IM MH - Acridines/chemical synthesis/metabolism/*pharmacology MH - Cell Cycle Checkpoints/drug effects MH - Cell Proliferation/*drug effects MH - Cell Survival/drug effects MH - Chemistry, Pharmaceutical MH - DNA/chemistry/metabolism MH - DNA Topoisomerases, Type I/*metabolism MH - DNA Topoisomerases, Type II/*metabolism MH - Dose-Response Relationship, Drug MH - HL-60 Cells MH - Hot Temperature MH - Humans MH - Leukemia, Promyelocytic, Acute/*drug therapy/enzymology/pathology MH - Membrane Potential, Mitochondrial/drug effects MH - Nucleic Acid Conformation MH - Nucleic Acid Denaturation MH - Spectrometry, Fluorescence MH - Spectrophotometry, Ultraviolet MH - Technology, Pharmaceutical/methods MH - Time Factors MH - Topoisomerase I Inhibitors/chemical synthesis/metabolism/*pharmacology MH - Topoisomerase II Inhibitors/chemical synthesis/metabolism/*pharmacology MH - Viscosity OTO - NOTNLM OT - Acridine derivatives OT - DNA-binding OT - HL-60 cells OT - Topoisomerases I and II EDAT- 2015/05/12 06:00 MHDA- 2016/03/10 06:00 CRDT- 2015/05/12 06:00 PHST- 2015/02/11 [received] PHST- 2015/04/04 [revised] PHST- 2015/04/25 [accepted] PHST- 2015/05/08 [aheadofprint] AID - S0928-0987(15)00178-5 [pii] AID - 10.1016/j.ejps.2015.04.023 [doi] PST - ppublish SO - Eur J Pharm Sci. 2015 Aug 30;76:192-202. doi: 10.1016/j.ejps.2015.04.023. Epub 2015 May 8. PMID- 25956843 OWN - NLM STAT- MEDLINE DA - 20150610 DCOM- 20160229 IS - 1872-7913 (Electronic) IS - 0924-8579 (Linking) VI - 46 IP - 1 DP - 2015 Jul TI - Aerosolised liposomal amphotericin B to prevent aspergillosis in acute myeloid leukaemia: Efficacy and cost effectiveness in real-life. PG - 82-7 LID - 10.1016/j.ijantimicag.2015.02.023 [doi] LID - S0924-8579(15)00122-3 [pii] AB - Chemotherapy-induced neutropenia can be complicated by invasive pulmonary aspergillosis (IPA). In 2008, liposomal amphotericin B (L-AmB) inhalation was shown to prevent IPA in a placebo-controlled trial. Patients with acute myeloid leukaemia (AML) are the subset of haematology patients at high risk for IPA. In 2008, L-AmB inhalation prophylaxis became the standard of care for all AML patients in Erasmus MC. In this study, the efficacy and cost effectiveness of L-AmB inhalation were evaluated in a prospective cohort of AML patients. In total, 127 consecutive AML patients received chemotherapy and prophylactically inhaled L-AmB during their first and second chemotherapy cycles; 108 patients treated for AML at the same sites from 2005-2008 served as controls. A standardised diagnostic protocol was used and probable/proven IPA served as the primary endpoint. Diagnostic and therapeutic costs were also comprehensively analysed and compared. A significant decrease in probable/proven IPA in the L-AmB inhalation group was observed (L-AmB 9.5% vs. controls 23.4%; P=0.0064). Systemic antifungal therapy given at any time during the entire AML therapy decreased from 52.8% to 29.9%. Per-patient equipment and drug costs for L-AmB inhalation (1292 euro/patient) were more than compensated for by a decrease in costs for diagnostics and therapeutic voriconazole use (-1816 euro/patient). No serious adverse events related to L-AmB inhalation were observed. In an unselected AML patient group, L-AmB inhalation resulted in a significant and substantial decrease in IPA and was cost saving. Now that azole resistance is more frequent, non-azole-based prophylaxis may become an attractive strategy. CI - Copyright (c) 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved. FAU - Chong, Ga-Lai M AU - Chong GL AD - Department of Haematology, Erasmus University Medical Center, PB 2040, 3000CA Rotterdam, The Netherlands; Department of Internal Medicine, Section of Infectious Diseases, Erasmus University Medical Center, PB 2040, 3000CA Rotterdam, The Netherlands. FAU - Broekman, Fleur AU - Broekman F AD - Department of Internal Medicine, Section of Infectious Diseases, Erasmus University Medical Center, PB 2040, 3000CA Rotterdam, The Netherlands. FAU - Polinder, Suzanne AU - Polinder S AD - Department of Public Health, Erasmus University Medical Center, PB 2040, 3000CA Rotterdam, The Netherlands. FAU - Doorduijn, Jeanette K AU - Doorduijn JK AD - Department of Haematology, Erasmus University Medical Center, PB 2040, 3000CA Rotterdam, The Netherlands. FAU - Lugtenburg, Pieternella J AU - Lugtenburg PJ AD - Department of Haematology, Erasmus University Medical Center, PB 2040, 3000CA Rotterdam, The Netherlands. FAU - Verbon, Annelies AU - Verbon A AD - Department of Internal Medicine, Section of Infectious Diseases, Erasmus University Medical Center, PB 2040, 3000CA Rotterdam, The Netherlands. FAU - Cornelissen, Jan J AU - Cornelissen JJ AD - Department of Haematology, Erasmus University Medical Center, PB 2040, 3000CA Rotterdam, The Netherlands. FAU - Rijnders, Bart J A AU - Rijnders BJ AD - Department of Internal Medicine, Section of Infectious Diseases, Erasmus University Medical Center, PB 2040, 3000CA Rotterdam, The Netherlands. Electronic address: b.rijnders@erasmusmc.nl. LA - eng PT - Clinical Study PT - Journal Article DEP - 20150415 PL - Netherlands TA - Int J Antimicrob Agents JT - International journal of antimicrobial agents JID - 9111860 RN - 0 (Aerosols) RN - 0 (Antifungal Agents) RN - 0 (liposomal amphotericin B) RN - 7XU7A7DROE (Amphotericin B) SB - IM MH - Administration, Inhalation MH - Adult MH - Aerosols/*administration & dosage/adverse effects/economics MH - Aged MH - Amphotericin B/*administration & dosage/adverse effects/economics MH - Antifungal Agents/*administration & dosage/adverse effects/economics MH - Aspergillosis/economics/*prevention & control MH - Chemoprevention/adverse effects/economics/*methods MH - Cost-Benefit Analysis MH - Diagnostic Tests, Routine/economics/methods MH - Drug-Related Side Effects and Adverse Reactions/epidemiology/pathology MH - Female MH - Humans MH - Leukemia, Myeloid, Acute/*complications MH - Male MH - Middle Aged MH - Netherlands MH - Prospective Studies MH - Treatment Outcome MH - Young Adult OTO - NOTNLM OT - Aerosolised liposomal amphotericin B OT - Cost effectiveness OT - Inhalation OT - Invasive pulmonary aspergillosis OT - Prophylaxis EDAT- 2015/05/10 06:00 MHDA- 2016/03/02 06:00 CRDT- 2015/05/10 06:00 PHST- 2014/10/13 [received] PHST- 2015/02/04 [revised] PHST- 2015/02/19 [accepted] PHST- 2015/04/15 [aheadofprint] AID - S0924-8579(15)00122-3 [pii] AID - 10.1016/j.ijantimicag.2015.02.023 [doi] PST - ppublish SO - Int J Antimicrob Agents. 2015 Jul;46(1):82-7. doi: 10.1016/j.ijantimicag.2015.02.023. Epub 2015 Apr 15. PMID- 25914345 OWN - NLM STAT- MEDLINE DA - 20150619 DCOM- 20160315 IS - 1099-0844 (Electronic) IS - 0263-6484 (Linking) VI - 33 IP - 4 DP - 2015 Jun TI - JNK and NFkappaB dependence of apoptosis induced by vinblastine in human acute promyelocytic leukaemia cells. PG - 211-9 LID - 10.1002/cbf.3105 [doi] AB - The relationship between the mitogen-activated protein kinase response, nuclear factor-kappaB (NFkappaB) expression and the apoptosis in human acute promyelocytic leukaemia NB4 cells treated with vinblastine was investigated in this work. Cell viability, subdiploid DNA and cell cycle were analysed by propidium iodide permeability and flow cytometry analyses. Apoptosis was determined by annexin V-Fluorescein isothiocyanate assays. Western-blot analysis was used for determination of expression levels of apoptotic factors (p53, Bax and Bcl2), intracellular kinases [serine/threonine-specific protein kinase, extracellular signal-regulated kinase and c-Jun N-terminal kinase (JNK)], NFkappaB factor and caspases. Electrophoretic mobility shift assay was usefully applied to study DNA-NFkappaB interaction. In NB4 cells, vinblastine produces alteration of p53 and DNA fragmentation. Vinblastine treatment had an antiproliferative effect via the induction of apoptosis producing Bax/Bcl-2 imbalance. Vinblastine treatment suppressed NFkappaB expression and depressed NFkappaB-DNA binding activity while maintaining JNK activation that subsequently resulted in apoptotic response through caspase-dependent pathway. Our study provides a possible anti-cancer mechanism of vinblastine action on NB4 cells by deregulation of the intracellular signalling cascade affecting to JNK activation and NFkappaB expression. Moreover, JNK activation and NFkappaB depression can be very significant factors in apoptosis induction by vinblastine. CI - Copyright (c) 2015 John Wiley & Sons, Ltd. FAU - Calvino, Eva AU - Calvino E AD - Unidad de Bioquimica y Biologia Molecular, Dpto. de Biologia de Sistemas, Facultad de Medicina y Ciencias de la Salud, Campus Universitario, Universidad de Alcala, Madrid, Spain. FAU - Tejedor, M Cristina AU - Tejedor MC AD - Unidad de Bioquimica y Biologia Molecular, Dpto. de Biologia de Sistemas, Facultad de Medicina y Ciencias de la Salud, Campus Universitario, Universidad de Alcala, Madrid, Spain. FAU - Sancho, Pilar AU - Sancho P AD - Unidad de Bioquimica y Biologia Molecular, Dpto. de Biologia de Sistemas, Facultad de Medicina y Ciencias de la Salud, Campus Universitario, Universidad de Alcala, Madrid, Spain. FAU - Herraez, Angel AU - Herraez A AD - Unidad de Bioquimica y Biologia Molecular, Dpto. de Biologia de Sistemas, Facultad de Medicina y Ciencias de la Salud, Campus Universitario, Universidad de Alcala, Madrid, Spain. FAU - Diez, Jose C AU - Diez JC AD - Unidad de Bioquimica y Biologia Molecular, Dpto. de Biologia de Sistemas, Facultad de Medicina y Ciencias de la Salud, Campus Universitario, Universidad de Alcala, Madrid, Spain. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150423 PL - England TA - Cell Biochem Funct JT - Cell biochemistry and function JID - 8305874 RN - 0 (Antineoplastic Agents, Phytogenic) RN - 0 (NF-kappa B) RN - 5V9KLZ54CY (Vinblastine) RN - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases) RN - EC 3.4.22.- (Caspases) SB - IM MH - Antineoplastic Agents, Phytogenic/*pharmacology MH - Apoptosis/*drug effects MH - Blotting, Western MH - Caspases/metabolism MH - Cell Cycle/drug effects MH - Cell Proliferation/drug effects MH - Electrophoretic Mobility Shift Assay MH - Flow Cytometry MH - Humans MH - JNK Mitogen-Activated Protein Kinases/*metabolism MH - Leukemia, Promyelocytic, Acute/*drug therapy/metabolism/*pathology MH - NF-kappa B/*metabolism MH - Tumor Cells, Cultured MH - Vinblastine/*pharmacology OTO - NOTNLM OT - Bax OT - Bcl-2 OT - JNK OT - NFkappaB OT - apoptosis OT - leukaemia OT - p53 OT - vinblastine EDAT- 2015/04/29 06:00 MHDA- 2016/03/16 06:00 CRDT- 2015/04/28 06:00 PHST- 2014/11/28 [received] PHST- 2015/03/18 [revised] PHST- 2015/03/18 [accepted] PHST- 2015/04/23 [aheadofprint] AID - 10.1002/cbf.3105 [doi] PST - ppublish SO - Cell Biochem Funct. 2015 Jun;33(4):211-9. doi: 10.1002/cbf.3105. Epub 2015 Apr 23. PMID- 25842225 OWN - NLM STAT- MEDLINE DA - 20150627 DCOM- 20160324 IS - 2152-2669 (Electronic) IS - 2152-2669 (Linking) VI - 15 IP - 7 DP - 2015 Jul TI - Oral Debio1143 (AT406), an antagonist of inhibitor of apoptosis proteins, combined with daunorubicin and cytarabine in patients with poor-risk acute myeloid leukemia--results of a phase I dose-escalation study. PG - 443-9 LID - 10.1016/j.clml.2015.02.020 [doi] LID - S2152-2650(15)00064-6 [pii] AB - BACKGROUND: Treatment of acute myeloid leukemia (AML) remains difficult owing to the development of treatment resistance, which might be overcome through antagonists of inhibitors of apoptosis proteins (IAPs). PATIENTS AND METHODS: The present multicenter, open-label, dose-escalation study aimed to evaluate the tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of Debio1143 (formerly AT-406), a new IAP antagonist, when given along with a standard "7 plus 3 regimen" of daunorubicin and cytarabine to poor-risk patients with AML during the induction cycle. Consecutive patient cohorts received once-daily 100, 200, 300, or 400 mg of oral Debio1143 on treatment days 1 to 5. Blood samples were collected regularly until hematologic recovery or response was documented. Bone marrow samples were collected on days 0, 14, and 29 and PK and PD samples on days 1, 3, 5, 8, and 10 and 1, 2, and 8, respectively. RESULTS: Of the 29 enrolled patients, 23 completed the study. The most common adverse events of any grade deemed related to treatment were nausea (31% of patients), diarrhea (14%), and febrile neutropenia (14%). Exposure exceeded dose proportionality, without accumulation over 5 days. Inhibition of cellular IAP1 was detectable in the CD34/CD117(+) cells and blasts. A total of 11 patients (38%) achieved complete remission, most in the 100-mg dose cohort. Of these, 6 (56%) developed a relapse within the study period. The patients with a response more frequently showed plasma increases of tumor necrosis factor-alpha and interleukin-8 after the first dose of Debio1143. CONCLUSION: Debio1143 /= 19) months. Three patients died within 60 days of enrollment (2 progressive disease, 1 non-dose-limiting toxicity, treatment-related). Pharmacokinetic data at 75 mg orally b.i.d. showed increased trough levels of midostaurin during cycle 2 compared with cycle 1 and persistent and increasing levels of its active metabolite, CGP52421. CONCLUSION: The combination of sequential azacitidine and midostaurin is safe and tolerable with response rates comparable with azacitidine alone and should be studied further in FLT3 mutation-positive AML. CI - Copyright (c) 2015 Elsevier Inc. All rights reserved. FAU - Cooper, Brenda W AU - Cooper BW AD - Department of Medicine, Seidman Cancer Center, University Hospitals, Case Medical Center, Cleveland, OH. Electronic address: brenda.cooper@uhhospitals.org. FAU - Kindwall-Keller, Tamila L AU - Kindwall-Keller TL AD - Department of Medicine, Seidman Cancer Center, University Hospitals, Case Medical Center, Cleveland, OH. FAU - Craig, Michael D AU - Craig MD AD - Hematopoietic Malignancy and Blood and Marrow Transplantation Program, Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, WV. FAU - Creger, Richard J AU - Creger RJ AD - Department of Medicine, Seidman Cancer Center, University Hospitals, Case Medical Center, Cleveland, OH. FAU - Hamadani, Mehdi AU - Hamadani M AD - Hematopoietic Malignancy and Blood and Marrow Transplantation Program, Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, WV. FAU - Tse, William W AU - Tse WW AD - Hematopoietic Malignancy and Blood and Marrow Transplantation Program, Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, WV. FAU - Lazarus, Hillard M AU - Lazarus HM AD - Department of Medicine, Seidman Cancer Center, University Hospitals, Case Medical Center, Cleveland, OH. LA - eng GR - P30 CA043703/CA/NCI NIH HHS/United States GR - P30 CA043703/CA/NCI NIH HHS/United States PT - Clinical Trial, Phase I PT - Journal Article PT - Multicenter Study PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20150216 PL - United States TA - Clin Lymphoma Myeloma Leuk JT - Clinical lymphoma, myeloma & leukemia JID - 101525386 RN - 0 (Antimetabolites, Antineoplastic) RN - 0 (Antineoplastic Agents) RN - 120685-11-2 (4'-N-benzoylstaurosporine) RN - EC 2.7.10.1 (fms-Like Tyrosine Kinase 3) RN - H88EPA0A3N (Staurosporine) RN - M801H13NRU (Azacitidine) SB - IM MH - Aged MH - Aged, 80 and over MH - Antimetabolites, Antineoplastic/administration & dosage/*therapeutic use MH - Antineoplastic Agents/administration & dosage/*therapeutic use MH - Antineoplastic Combined Chemotherapy Protocols MH - Azacitidine/administration & dosage/*therapeutic use MH - Female MH - Humans MH - Leukemia, Myeloid, Acute/*drug therapy MH - Male MH - Middle Aged MH - Mutation MH - Neoplasm Recurrence, Local/*drug therapy MH - Staurosporine/administration & dosage/*analogs & derivatives/therapeutic use MH - Treatment Outcome MH - fms-Like Tyrosine Kinase 3/antagonists & inhibitors/genetics PMC - PMC4484305 MID - NIHMS675731 OID - NLM: NIHMS675731 [Available on 07/01/16] OID - NLM: PMC4484305 [Available on 07/01/16] OTO - NOTNLM OT - Azacitidine OT - Elderly AML OT - FLT3 inhibitor OT - Midostaurin EDAT- 2015/03/18 06:00 MHDA- 2016/03/25 06:00 CRDT- 2015/03/18 06:00 PMCR- 2016/07/01 00:00 PHST- 2014/12/12 [received] PHST- 2015/01/21 [revised] PHST- 2015/02/03 [accepted] PHST- 2015/02/16 [aheadofprint] AID - S2152-2650(15)00046-4 [pii] AID - 10.1016/j.clml.2015.02.017 [doi] PST - ppublish SO - Clin Lymphoma Myeloma Leuk. 2015 Jul;15(7):428-432.e2. doi: 10.1016/j.clml.2015.02.017. Epub 2015 Feb 16. PMID- 25749041 OWN - NLM STAT- MEDLINE DA - 20150408 DCOM- 20160229 LR - 20150623 IS - 1949-2553 (Electronic) IS - 1949-2553 (Linking) VI - 6 IP - 8 DP - 2015 Mar 20 TI - Efficacy and safety of decitabine in combination with G-CSF, low-dose cytarabine and aclarubicin in newly diagnosed elderly patients with acute myeloid leukemia. PG - 6448-58 AB - PURPOSE: This prospective phase II, open label, study was designed to assess the efficacy and safety of D-CAG induction treatment for elderly patients with newly diagnosed AML. EXPERIMENTAL DESIGN: All patients in this study were treated with decitabine of 15 mg/m2 for 5 days and G-CSF for priming, in combination with cytarabine of 10-mg/m2 q12h for 7 days and aclarubicin of 10 mg/day for 4 days (D-CAG). RESULTS: Among 85 evaluable patients, overall response rate (ORR) and complete remission (CR) were 82.4% and 64.7%, respectively, after 1 cycle of therapy. The ORR in patients aged <70 years was 83.0% and 81.6% in patients aged >/=70 years. There was a significantly longer median overall survival (OS) in patients with response (16 months) than in those without response (7 months, p< 0.0001). The OS for patients aged >/=70 years and 60-69 years was 10 months and 12 months, respectively (p=0.4994). The two-year OS probability was 19.2% and the twenty-month survival rate was 33.8%. Induction mortality of D-CAG treated elderly patients with AML is 4.4%. CONCLUSION: D-CAG regimen was well tolerated and showed a promising clinic efficacy in elderly patients with AML (>/=70 years). FAU - Li, Jianyong AU - Li J AD - First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China. AD - Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China. FAU - Chen, Yaoyu AU - Chen Y AD - First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China. AD - Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China. FAU - Zhu, Yu AU - Zhu Y AD - First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China. AD - Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China. FAU - Zhou, Jianfeng AU - Zhou J AD - Tongji Hospital affiliated to Tongji medical college of Huazhong University of Science and Technology, Wuhan, China. FAU - Xu, Yanli AU - Xu Y AD - Nanjing Hospital Affiliated to Nanjing Medical University, Nanjing, China. FAU - Li, Yan AU - Li Y AD - First Affiliated Hospital of China Medical University, Shenyang, China. FAU - Yu, Kang AU - Yu K AD - First Affiliated Hospital of Wenzhou Medical College, Wenzhou, China. FAU - Pan, Ling AU - Pan L AD - West China Hospital of Sichuan University, Chengdu, China. FAU - Wang, Jianmin AU - Wang J AD - Changhai Hospital, Secondary Military Medical University, Shanghai, China. FAU - Ding, Jiahua AU - Ding J AD - Zhongda Hospital, Southeast University, Nanjing, China. FAU - Gu, Jian AU - Gu J AD - Clinic Medical College of Yangzhou University, Yangzhou, China. FAU - Zhou, Shanhua AU - Zhou S AD - Zhongshan Hospital, Fudan University, Shanghai, China. FAU - Shi, Jinning AU - Shi J AD - Jiangning Hospital, Nanjing, China. FAU - Hong, Ming AU - Hong M AD - First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China. AD - Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China. FAU - Xu, Ji AU - Xu J AD - First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China. AD - Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China. FAU - Pan, Liangqin AU - Pan L AD - First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China. AD - Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China. FAU - Duan, Limin AU - Duan L AD - First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China. AD - Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China. FAU - Zhang, Run AU - Zhang R AD - First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China. AD - Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China. FAU - Zhang, Sujiang AU - Zhang S AD - First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China. AD - Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China. FAU - Zhu, Huayuan AU - Zhu H AD - First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China. AD - Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China. FAU - Lu, Hua AU - Lu H AD - First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China. AD - Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China. FAU - Liu, Peng AU - Liu P AD - First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China. AD - Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China. FAU - Qiu, Hongxia AU - Qiu H AD - First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China. AD - Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China. FAU - Wu, Hanxin AU - Wu H AD - First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China. AD - Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China. FAU - Qian, Sixuan AU - Qian S AD - First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China. AD - Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China. LA - eng PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't PL - United States TA - Oncotarget JT - Oncotarget JID - 101532965 RN - 04079A1RDZ (Cytarabine) RN - 143011-72-7 (Granulocyte Colony-Stimulating Factor) RN - 74KXF8I502 (Aclarubicin) RN - 776B62CQ27 (decitabine) RN - M801H13NRU (Azacitidine) RN - CAG protocol SB - IM MH - Aclarubicin/administration & dosage MH - Aged MH - Aged, 80 and over MH - Antineoplastic Combined Chemotherapy Protocols/administration & dosage/adverse effects/*therapeutic use MH - Azacitidine/administration & dosage/analogs & derivatives MH - Cytarabine/administration & dosage MH - Female MH - Granulocyte Colony-Stimulating Factor/administration & dosage MH - Humans MH - Leukemia, Myeloid, Acute/*drug therapy MH - Male MH - Prospective Studies MH - Survival Analysis MH - Treatment Outcome PMC - PMC4467448 OID - NLM: PMC4467448 OTO - NOTNLM OT - AML OT - D-CAG OT - elderly patients EDAT- 2015/03/10 06:00 MHDA- 2016/03/02 06:00 CRDT- 2015/03/10 06:00 PHST- 2014/12/01 [received] PHST- 2015/01/13 [accepted] AID - 3361 [pii] AID - 10.18632/oncotarget.3361 [doi] PST - ppublish SO - Oncotarget. 2015 Mar 20;6(8):6448-58. PMID- 25639656 OWN - NLM STAT- MEDLINE DA - 20150817 DCOM- 20160307 IS - 1743-7563 (Electronic) IS - 1743-7555 (Linking) VI - 11 IP - 3 DP - 2015 Sep TI - Long-term outcomes for patients with acute myeloid leukemia: a single-center experience from AIIMS, India. PG - 242-52 LID - 10.1111/ajco.12333 [doi] AB - AIM: To analyze clinicopathological characteristics of acute myeloid leukemia (AML) patients and to evaluate long-term outcome of these patients presented to single tertiary care center in India. METHODS: We evaluated outcomes of 480 patients (age 8-60 years), classified into good, intermediate and poor risk according to cytogenetic results. Standard "3 + 7" induction therapy with dose of daunorubicin ranging from 45 to 90 mg/m(2) followed by two to three courses of high-dose cytarabine (12-18 g/m(2) ) as consolidation therapy was given to majority. RESULTS: The complete remission rate of the treated population (407 patients) was 70% with 84.8% in good risk, 67.9% in intermediate risk and 54.2% in poor risk (P = 0.0001). Induction mortality was 18.4%. One hundred twenty-nine patients relapsed with median treatment free interval of 10.4 months. At a median follow-up of 34.5 months, the median overall survival (OS) was 20.6 months with an estimated 5-year survival rate of 35.5%. No difference was found in OS between the three risk groups; however, patients with intermediate risk had a better leukemia-free survival (LFS) in comparison to good risk. Multivariate analysis showed age, performance status, treatment completion and hematopoietic stem cell transplant affecting OS, while only treatment completion affected LFS. CONCLUSION: This is one of the largest single-center studies reflecting more accurately the outcome of AML in India. These results are likely due to uniform treatment protocols, intensification of induction and post-remission treatments with comprehensive supportive care. CI - (c) 2015 Wiley Publishing Asia Pty Ltd. FAU - Bahl, Ankur AU - Bahl A AD - Department of Medical Oncology, Dr. B. R. A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India. FAU - Sharma, Atul AU - Sharma A AD - Department of Medical Oncology, Dr. B. R. A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India. FAU - Raina, Vinod AU - Raina V AD - Department of Medical Oncology, Dr. B. R. A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India. FAU - Kumar, Lalit AU - Kumar L AD - Department of Medical Oncology, Dr. B. R. A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India. FAU - Bakhshi, Sameer AU - Bakhshi S AD - Department of Medical Oncology, Dr. B. R. A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India. FAU - Gupta, Ritu AU - Gupta R AD - Department of Laboratory Oncology, Dr. B. R. A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India. FAU - Kumar, Rajeev AU - Kumar R AD - Department of Laboratory Oncology, Dr. B. R. A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India. LA - eng PT - Journal Article DEP - 20150130 PL - Australia TA - Asia Pac J Clin Oncol JT - Asia-Pacific journal of clinical oncology JID - 101241430 RN - 04079A1RDZ (Cytarabine) RN - ZS7284E0ZP (Daunorubicin) SB - IM MH - Adolescent MH - Adult MH - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use MH - Child MH - Cytarabine/administration & dosage/*therapeutic use MH - Daunorubicin/administration & dosage/*therapeutic use MH - Female MH - Humans MH - India MH - Leukemia, Myeloid, Acute/*drug therapy/mortality MH - Male MH - Middle Aged MH - Remission Induction MH - Survival Rate MH - Treatment Outcome MH - Young Adult OTO - NOTNLM OT - acute myeloid leukemia OT - cytogenetic OT - outcome OT - prognostic factor OT - survival EDAT- 2015/02/03 06:00 MHDA- 2016/03/08 06:00 CRDT- 2015/02/03 06:00 PHST- 2014/10/15 [accepted] PHST- 2015/01/30 [aheadofprint] AID - 10.1111/ajco.12333 [doi] PST - ppublish SO - Asia Pac J Clin Oncol. 2015 Sep;11(3):242-52. doi: 10.1111/ajco.12333. Epub 2015 Jan 30. PMID- 25631637 OWN - NLM STAT- MEDLINE DA - 20150706 DCOM- 20160322 LR - 20150710 IS - 1532-1681 (Electronic) IS - 0268-960X (Linking) VI - 29 IP - 4 DP - 2015 Jul TI - An ATRActive future for differentiation therapy in AML. PG - 263-8 LID - 10.1016/j.blre.2015.01.002 [doi] LID - S0268-960X(15)00004-1 [pii] AB - The success of all-trans retinoic acid (ATRA) therapy in acute promeylocytic leukemia (APL) has spawned numerous attempts to translate the paradigm of differentiation therapy to non-APL acute myelocytic leukemia (AML). However, the results of clinical trials have been overall disappointing. In this review we discuss the mechanism of retinoic acid signaling and the results of major clinical trials that have attempted to incorporate ATRA into AML regimens. We discuss recent evidence that indicate that the retinoic acid signaling pathway may be dysfunctional in AML. Preliminary studies suggest that targeting the pathways that modify retinoic acid receptor activity may reactivate the dormant retinoic acid-signaling pathway. Such strategies may revive the ability of ATRA to induce myeloid differentiation and apoptosis in non-APL AML. CI - Copyright (c) 2015 Elsevier Ltd. All rights reserved. FAU - Johnson, Daniel E AU - Johnson DE AD - Department of Medicine and University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh PA 15213 USA. FAU - Redner, Robert L AU - Redner RL AD - Department of Medicine and University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh PA 15213 USA. Electronic address: redner@pitt.edu. LA - eng GR - P30 CA047904/CA/NCI NIH HHS/United States GR - P30 CA047904/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20150121 PL - England TA - Blood Rev JT - Blood reviews JID - 8708558 RN - 0 (Antineoplastic Agents) RN - 5688UTC01R (Tretinoin) SB - IM MH - Antineoplastic Agents/*therapeutic use MH - Apoptosis MH - Cell Differentiation MH - Humans MH - Leukemia, Myeloid, Acute/*drug therapy MH - Signal Transduction MH - Tretinoin/*therapeutic use PMC - PMC4494875 MID - NIHMS657395 OID - NLM: NIHMS657395 [Available on 07/01/16] OID - NLM: PMC4494875 [Available on 07/01/16] OTO - NOTNLM OT - AML OT - ATRA OT - differentiation therapy EDAT- 2015/01/30 06:00 MHDA- 2016/03/24 06:00 CRDT- 2015/01/30 06:00 PMCR- 2016/07/01 00:00 PHST- 2014/10/09 [received] PHST- 2015/01/13 [accepted] PHST- 2015/01/21 [aheadofprint] AID - S0268-960X(15)00004-1 [pii] AID - 10.1016/j.blre.2015.01.002 [doi] PST - ppublish SO - Blood Rev. 2015 Jul;29(4):263-8. doi: 10.1016/j.blre.2015.01.002. Epub 2015 Jan 21. PMID- 25624175 OWN - NLM STAT- MEDLINE DA - 20150606 DCOM- 20160301 IS - 1879-0461 (Electronic) IS - 1040-8428 (Linking) VI - 95 IP - 1 DP - 2015 Jul TI - Prognostic and therapeutic implications of early treatment response assessment in acute myeloid leukemia. PG - 38-45 LID - 10.1016/j.critrevonc.2015.01.005 [doi] LID - S1040-8428(15)00006-2 [pii] AB - Early assessment of disease response to induction chemotherapy is important in acute myeloid leukemia (AML) in order to plan future therapy and identify chemorefractory disease. Such assessment is customarily performed by examining the bone marrow at around day 14 after initiation of chemotherapy. However, criteria for assessment of residual leukemia in day 14 bone marrow specimens as well as the significance of partial response on long term outcomes remain unclear. Clinical practices vary regarding the therapeutic intervention for residual disease and include readministration of the original induction therapy or use of a different reinduction regimen. In this article, we critically examine the prognostic significance of residual disease detected on interim bone marrow examination as well as data on reinduction therapy with the original induction regimen versus an alternate regimen. We emphasize the need for standardizing reporting of interim bone marrow assessment as well as evaluating new technologies and biomarkers for early assessment of disease response and chemosensitivity in AML. CI - Copyright (c) 2015 Elsevier Ireland Ltd. All rights reserved. FAU - Pullarkat, Vinod AU - Pullarkat V AD - Department of Hematology and Hematopoietic Cell Transplantation, City of Hope Medical Center, 1500, Duarte, CA 91010, United States. Electronic address: vpullarkat@coh.org. FAU - Aldoss, Ibrahim AU - Aldoss I AD - Department of Hematology and Hematopoietic Cell Transplantation, City of Hope Medical Center, 1500, Duarte, CA 91010, United States. LA - eng PT - Journal Article PT - Review DEP - 20150115 PL - Netherlands TA - Crit Rev Oncol Hematol JT - Critical reviews in oncology/hematology JID - 8916049 SB - IM MH - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use MH - Bone Marrow/*drug effects/*pathology MH - Humans MH - Induction Chemotherapy/*methods MH - Leukemia, Myeloid, Acute/*diagnosis/*drug therapy/pathology MH - Neoplasm, Residual/diagnosis/drug therapy/pathology MH - Prognosis OTO - NOTNLM OT - Acute myeloid leukemia OT - Chemosensitivity OT - Day 14 bone marrow OT - Early response OT - Reinduction EDAT- 2015/01/28 06:00 MHDA- 2016/03/02 06:00 CRDT- 2015/01/28 06:00 PHST- 2014/09/23 [received] PHST- 2014/11/27 [revised] PHST- 2015/01/08 [accepted] PHST- 2015/01/15 [aheadofprint] AID - S1040-8428(15)00006-2 [pii] AID - 10.1016/j.critrevonc.2015.01.005 [doi] PST - ppublish SO - Crit Rev Oncol Hematol. 2015 Jul;95(1):38-45. doi: 10.1016/j.critrevonc.2015.01.005. Epub 2015 Jan 15. PMID- 25609058 OWN - NLM STAT- MEDLINE DA - 20150402 DCOM- 20160301 LR - 20150404 IS - 1078-0432 (Print) IS - 1078-0432 (Linking) VI - 21 IP - 7 DP - 2015 Apr 1 TI - DNMT3A Mutational Status Affects the Results of Dose-Escalated Induction Therapy in Acute Myelogenous Leukemia. PG - 1614-20 LID - 10.1158/1078-0432.CCR-14-0327 [doi] AB - PURPOSE: DNA methyltransferase 3A (DNMT3A) is one of the commonly mutated genes in acute myelogenous leukemia (AML). Reports on the prognostic significance of DNMT3A mutations have been inconsistent, and most of the data are available only for patients 60 years of age or younger. We hypothesized that this inconsistency is due to an interaction between the dose of anthracycline used in induction therapy and DNMT3A status. We studied whether patients with DNMT3A-mutated AML treated with standard dose anthracyclines had an inferior survival compared with patients with other mutation profiles or those who received high-dose therapy. EXPERIMENTAL DESIGN: A total of 152 patients in this retrospective cohort study (median age, 54 years) with de novo AML underwent induction therapy and next-generation sequencing of 33 commonly mutated genes in hematologic malignancies, including DNMT3A, FLT3-ITD, NPM1, and IDH1/2. Cox regression was used to know whether those with DNMT3A mutations who were treated with standard dose anthracycline had inferior survival. RESULTS: DNMT3A mutations, found in 32% of patients, were not associated with an inferior survival. Dose escalation of anthracycline in the induction regimen was associated with improved survival in those with DNMT3A mutations but not those with wild-type DNMT3A. Patients with DNMT3A mutations who received standard dose induction had shorter survival time than other patient groups (10.1 months vs. 19.8 months, P = 0.0129). This relationship remained significant (HR, 1.90; P = 0.006) controlling for multiple variables. CONCLUSIONS: Patients with DNMT3A-mutated AML have an inferior survival when treated with standard-dose anthracycline induction therapy. This group should be considered for high-dose induction therapy. CI - (c)2015 American Association for Cancer Research. FAU - Sehgal, Alison R AU - Sehgal AR AD - Division of Hematology and Oncology, University of Pittsburgh, Pittsburgh, Pennsylvania. FAU - Gimotty, Phyllis A AU - Gimotty PA AD - Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania. FAU - Zhao, Jianhua AU - Zhao J AD - Division of Hematology and Oncology, University of Pennsylvania, Philadelphia, Pennsylvania. Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. FAU - Hsu, Jing-Mei AU - Hsu JM AD - Division of Hematology and Oncology, University of Pennsylvania, Philadelphia, Pennsylvania. FAU - Daber, Robert AU - Daber R AD - Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. FAU - Morrissette, Jennifer D AU - Morrissette JD AD - Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. FAU - Luger, Selina AU - Luger S AD - Division of Hematology and Oncology, University of Pennsylvania, Philadelphia, Pennsylvania. FAU - Loren, Alison W AU - Loren AW AD - Division of Hematology and Oncology, University of Pennsylvania, Philadelphia, Pennsylvania. FAU - Carroll, Martin AU - Carroll M AD - Division of Hematology and Oncology, University of Pennsylvania, Philadelphia, Pennsylvania. carroll2@mail.med.upenn.edu. LA - eng GR - 1R01CA149566/CA/NCI NIH HHS/United States GR - R01 CA149566/CA/NCI NIH HHS/United States GR - R21 CA185365/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20150121 PL - United States TA - Clin Cancer Res JT - Clinical cancer research : an official journal of the American Association for Cancer Research JID - 9502500 RN - 0 (Anthracyclines) RN - 0 (Antineoplastic Agents) RN - EC 2.1.1.37 (DNA (Cytosine-5-)-Methyltransferase) RN - EC 2.1.1.37 (DNA methyltransferase 3A) SB - IM MH - Adult MH - Aged MH - Anthracyclines/administration & dosage MH - Antineoplastic Agents/administration & dosage MH - Cohort Studies MH - DNA (Cytosine-5-)-Methyltransferase/*genetics MH - DNA Mutational Analysis MH - Female MH - High-Throughput Nucleotide Sequencing MH - Humans MH - Induction Chemotherapy/*methods MH - Kaplan-Meier Estimate MH - Leukemia, Myeloid, Acute/*drug therapy/*genetics/*mortality MH - Male MH - Middle Aged MH - Proportional Hazards Models MH - Retrospective Studies MH - Young Adult PMC - PMC4383675 MID - NIHMS657697 OID - NLM: NIHMS657697 [Available on 04/01/16] OID - NLM: PMC4383675 [Available on 04/01/16] EDAT- 2015/01/23 06:00 MHDA- 2016/03/02 06:00 CRDT- 2015/01/23 06:00 PMCR- 2016/04/01 00:00 PHST- 2014/02/14 [received] PHST- 2014/12/11 [accepted] PHST- 2015/01/21 [aheadofprint] AID - 1078-0432.CCR-14-0327 [pii] AID - 10.1158/1078-0432.CCR-14-0327 [doi] PST - ppublish SO - Clin Cancer Res. 2015 Apr 1;21(7):1614-20. doi: 10.1158/1078-0432.CCR-14-0327. Epub 2015 Jan 21. PMID- 25585874 OWN - NLM STAT- MEDLINE DA - 20150224 DCOM- 20160324 IS - 1791-3004 (Electronic) IS - 1791-2997 (Linking) VI - 11 IP - 5 DP - 2015 May TI - Promoter DNA methylation and expression levels of HOXA4, HOXA5 and MEIS1 in acute myeloid leukemia. PG - 3948-54 LID - 10.3892/mmr.2015.3196 [doi] AB - HOXA genes encode transcription factors, which are crucial for embryogenesis and tissue differentiation and are involved in the early stages of hematopoiesis. Aberrations in HOXA genes and their cofactor MEIS1 are found in human neoplasms, including acute myeloid leukemia (AML). The present study investigated the role of HOXA4, HOXA5 and MEIS1 promoter DNA methylation and mRNA expression in AML. Samples from 78 AML patients and 12 normal bone marrow (BM) samples were included. The levels of promoter DNA methylation were determined using quantitative methylationspecific polymerase chain reaction (PCR; qMSP) and the relative expression levels were measured using reverse transcription quantitative PCR in Ficollseparated BM mononuclear cells and in fluorescent activated cell sortingsorted populations of normal hematopoietic progenitors. In total, 38.1 and 28.9% of the patients exhibited high methylation levels of HOXA4 and HOXA5, respectively, compared with the control samples, and MEIS1 methylation was almost absent. An inverse correlation between HOXA4 methylation and expression was identified in a group of patients with a normal karyotype (NK AML). An association between the genes was observed and correlation between the DNA methylation and expression levels of the HOXA gene promoter with the expression of MEIS1 was observed. Patients with favorable chromosomal aberrations revealed a low level of HOXA4 methylation and decreased expression levels of HOXA5 and MEIS1 compared with the NK AML and the adverse cytogenetic risk patients. The NK AML patients with NPM1 mutations exhibited elevated HOXA4 methylation and expression levels of HOXA5 and MEIS1 compared with the NPM1 wildtype patients. Comparison of the undifferentiated BMderived hematopoietic CD34+CD38low, CD34+CD38+ and CD15+ cells revealed a gradual decrease in the expression levels of these three genes and an increase in HOXA4 promoter methylation. This differentiationassociated variability was not observed in AML, which was classified according to the FrenchAmericanBritish system. FAU - Musialik, Ewa AU - Musialik E AD - Department of Molecular and Translational Oncology, Maria SklodowskaCurie Memorial Cancer Center and Institute of Oncology, Warsaw 02781, Poland. FAU - Bujko, Mateusz AU - Bujko M AD - Department of Molecular and Translational Oncology, Maria SklodowskaCurie Memorial Cancer Center and Institute of Oncology, Warsaw 02781, Poland. FAU - Kober, Paulina AU - Kober P AD - Department of Molecular and Translational Oncology, Maria SklodowskaCurie Memorial Cancer Center and Institute of Oncology, Warsaw 02781, Poland. FAU - Grygorowicz, Monika Anna AU - Grygorowicz MA AD - Department of Immunology, Maria SklodowskaCurie Memorial Cancer Center and Institute of Oncology, Warsaw 02781, Poland. FAU - Libura, Marta AU - Libura M AD - Department of Hematology, Oncology and Internal Diseases, The Medical University of Warsaw, Warsaw 02097, Poland. FAU - Przestrzelska, Marta AU - Przestrzelska M AD - Department of Hematology, Oncology and Internal Diseases, The Medical University of Warsaw, Warsaw 02097, Poland. FAU - Juszczynski, Przemyslaw AU - Juszczynski P AD - Department of Diagnostic Hematology, Institute of Hematology and Transfusion Medicine, Warsaw 02109, Poland. FAU - Borg, Katarzyna AU - Borg K AD - Department of Diagnostic Hematology, Institute of Hematology and Transfusion Medicine, Warsaw 02109, Poland. FAU - Florek, Izabela AU - Florek I AD - Department of Hematology, Jagiellonian University, Cracow 31501, Poland. FAU - Jakobczyk, Malgorzata AU - Jakobczyk M AD - Department of Hematology, Jagiellonian University, Cracow 31501, Poland. FAU - Siedlecki, Janusz Aleksander AU - Siedlecki JA AD - Department of Molecular and Translational Oncology, Maria SklodowskaCurie Memorial Cancer Center and Institute of Oncology, Warsaw 02781, Poland. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150113 PL - Greece TA - Mol Med Rep JT - Molecular medicine reports JID - 101475259 RN - 0 (HOXA5 protein, human) RN - 0 (Homeodomain Proteins) RN - 0 (Neoplasm Proteins) RN - 0 (Nuclear Proteins) RN - 0 (RNA, Messenger) RN - 0 (myeloid ecotropic viral integration site 1 protein) RN - 117896-08-9 (nucleophosmin) RN - 127609-92-1 (HOXA4 protein, human) RN - EC 2.7.10.1 (fms-Like Tyrosine Kinase 3) SB - IM MH - Adult MH - Aged MH - Bone Marrow Cells/metabolism/pathology MH - Case-Control Studies MH - Chromosome Aberrations MH - *DNA Methylation MH - Female MH - *Gene Expression Regulation, Leukemic MH - Homeodomain Proteins/*genetics/metabolism MH - Humans MH - Immunophenotyping MH - Leukemia, Myeloid, Acute/diagnosis/*genetics/metabolism MH - Male MH - Middle Aged MH - Mutation MH - Neoplasm Proteins/*genetics/metabolism MH - Nuclear Proteins/genetics MH - *Promoter Regions, Genetic MH - RNA, Messenger/genetics MH - fms-Like Tyrosine Kinase 3/genetics EDAT- 2015/01/15 06:00 MHDA- 2016/03/25 06:00 CRDT- 2015/01/15 06:00 PHST- 2014/02/14 [received] PHST- 2014/11/03 [accepted] PHST- 2015/01/13 [aheadofprint] AID - 10.3892/mmr.2015.3196 [doi] PST - ppublish SO - Mol Med Rep. 2015 May;11(5):3948-54. doi: 10.3892/mmr.2015.3196. Epub 2015 Jan 13. PMID- 25545192 OWN - NLM STAT- MEDLINE DA - 20150128 DCOM- 20160322 IS - 1743-7563 (Electronic) IS - 1743-7555 (Linking) VI - 11 IP - 1 DP - 2015 Mar TI - Treatment of elderly patients with acute myeloid leukemia with azacitidine results in fewer hospitalization days and infective complications but similar survival compared with intensive chemotherapy. PG - 54-61 LID - 10.1111/ajco.12331 [doi] AB - AIMS: Azacitidine has been shown to prolong overall survival (OS) compared with best supportive care in elderly patients with acute myeloid leukemia (AML) with low blast counts but it is unknown if azacitidine has a similar efficacy in patients with blast counts of >30%. It is also unknown if azacitidine is comparable to intensive chemotherapy in terms of survival and morbidity. METHODS: Differences between the outcomes of elderly AML patients who received intensive chemotherapy, azacitidine-based therapy or best supportive care are studied in this retrospective review. Patients 60 years or older diagnosed with AML between January 2009 and June 2011 were included. Those who passed away within less than 2 weeks of diagnosis were excluded. RESULTS: At a median follow-up of 7.2 months (range: 0.5-26.4 months), estimated median OS for patients who received azacitidine-based therapy was 9.8 months (range: 2.4-22.5 months) compared with 8.9 months (range: 0.9-26.4 months) for patients who received intensive chemotherapy (P=0.89). Compared with azacitidine-based therapy, intensive chemotherapy is associated with more inpatient days and episodes of febrile illness requiring inpatient stay or intravenous antibiotics. CONCLUSIONS: Compared with intensive chemotherapy in elderly patients with AML, azacitidine-based therapy is associated with similar median survival but lower number of hospitalization days and infective episodes. CI - (c) 2014 Wiley Publishing Asia Pty Ltd. FAU - Lao, Zhentang AU - Lao Z AD - Department of Hematology, Singapore General Hospital, Singapore. FAU - Yiu, Richard AU - Yiu R FAU - Wong, Gee Chuan AU - Wong GC FAU - Ho, Aloysius AU - Ho A LA - eng PT - Comparative Study PT - Journal Article DEP - 20141228 PL - Australia TA - Asia Pac J Clin Oncol JT - Asia-Pacific journal of clinical oncology JID - 101241430 RN - 04079A1RDZ (Cytarabine) RN - M801H13NRU (Azacitidine) RN - ZRP63D75JW (Idarubicin) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use MH - Azacitidine/administration & dosage MH - Cytarabine/administration & dosage MH - Female MH - Follow-Up Studies MH - Hospitalization/*statistics & numerical data MH - Humans MH - Idarubicin/administration & dosage MH - Infection/chemically induced/*mortality MH - Leukemia, Myeloid, Acute/*complications/drug therapy/*mortality/pathology MH - Male MH - Middle Aged MH - Neoplasm Staging MH - Retrospective Studies MH - Survival Rate MH - Treatment Outcome OTO - NOTNLM OT - acute myeloid leukemia OT - azacitidine OT - elderly EDAT- 2014/12/30 06:00 MHDA- 2016/03/24 06:00 CRDT- 2014/12/30 06:00 PHST- 2014/10/15 [accepted] PHST- 2014/12/28 [aheadofprint] AID - 10.1111/ajco.12331 [doi] PST - ppublish SO - Asia Pac J Clin Oncol. 2015 Mar;11(1):54-61. doi: 10.1111/ajco.12331. Epub 2014 Dec 28. PMID- 25523507 OWN - NLM STAT- MEDLINE DA - 20151113 DCOM- 20160229 LR - 20160303 IS - 1097-0215 (Electronic) IS - 0020-7136 (Linking) VI - 137 IP - 5 DP - 2015 Sep 1 TI - High IDH1 expression is associated with a poor prognosis in cytogenetically normal acute myeloid leukemia. PG - 1058-65 LID - 10.1002/ijc.29395 [doi] AB - The prognostic value of IDH1 mutations has been systematically evaluated in acute myeloid leukemia (AML) patients recently. However, the role of IDH1 expression in AML is still under exploration. To investigate the clinical significance, we analyzed the IDH1/2 expression in 320 patients with cytogenetically normal AML (CN-AML) by quantitative real-time reverse-transcription polymerase chain reaction. High expression of IDH1 was predominant in patients with FLT3-ITD and DNMT3A mutations and less prevalent in cases with CEBPA double allele mutations. Strong association was observed between high IDH1 expression and low expression of microRNA 181 family. Prognosis was adversely affected by high IDH1 expression, with shorter overall survival and event-free survival in the context of clinical characteristics, including age, WBC count, and gene mutations of NPM1, FLT3-ITD, CEBPA, IDH1, IDH2 and DNMT3A in CN-AML. Moreover, the clinical outcome of IDH1 expression in terms of overall survival, event-free survival and complete remission rate still remained in multivariate models in CN-AML. Importantly, the prognostic value was validated using the published microarray data from 79 adult patients treated according to the German AMLCG-1999 protocol. Our results demonstrated that high IDH1 expression is associated with a poor prognosis of CN-AML. CI - (c) 2014 UICC. FAU - Ma, Qiu-Ling AU - Ma QL AD - Department of Hematology and Institute of Hematology, The First Affiliated Hospital, Zhejiang University, Hangzhou, China. AD - Key Laboratory of Hematopoietic Malignancies, Hangzhou, Zhejiang Province, People's Republic of China. AD - Department of Hematology, The Second Affiliated Hospital of Henan College of Traditional Chinese Medicine, Zhengzhou, China. FAU - Wang, Jing-Han AU - Wang JH AD - Department of Hematology and Institute of Hematology, The First Affiliated Hospital, Zhejiang University, Hangzhou, China. AD - Key Laboratory of Hematopoietic Malignancies, Hangzhou, Zhejiang Province, People's Republic of China. FAU - Wang, Yun-Gui AU - Wang YG AD - Department of Hematology and Institute of Hematology, The First Affiliated Hospital, Zhejiang University, Hangzhou, China. FAU - Hu, Chao AU - Hu C AD - Department of Hematology and Institute of Hematology, The First Affiliated Hospital, Zhejiang University, Hangzhou, China. FAU - Mu, Qi-Tian AU - Mu QT AD - Department of Hematology and Institute of Hematology, The First Affiliated Hospital, Zhejiang University, Hangzhou, China. FAU - Yu, Meng-Xia AU - Yu MX AD - Department of Hematology and Institute of Hematology, The First Affiliated Hospital, Zhejiang University, Hangzhou, China. FAU - Wang, Lei AU - Wang L AD - Department of Hematology and Institute of Hematology, The First Affiliated Hospital, Zhejiang University, Hangzhou, China. FAU - Wang, Dong-Mei AU - Wang DM AD - Department of Hematology and Institute of Hematology, The First Affiliated Hospital, Zhejiang University, Hangzhou, China. FAU - Yang, Min AU - Yang M AD - Department of Hematology and Institute of Hematology, The First Affiliated Hospital, Zhejiang University, Hangzhou, China. FAU - Yin, Xiu-Feng AU - Yin XF AD - Department of Hematology and Institute of Hematology, The First Affiliated Hospital, Zhejiang University, Hangzhou, China. FAU - Chen, Fei-Fei AU - Chen FF AD - Department of Hematology and Institute of Hematology, The First Affiliated Hospital, Zhejiang University, Hangzhou, China. FAU - Lu, Sha-Sha AU - Lu SS AD - Department of Hematology and Institute of Hematology, The First Affiliated Hospital, Zhejiang University, Hangzhou, China. FAU - Chen, Jian AU - Chen J AD - Department of Hematology and Institute of Hematology, The First Affiliated Hospital, Zhejiang University, Hangzhou, China. FAU - Zhu, Zhi-Juan AU - Zhu ZJ AD - Department of Hematology and Institute of Hematology, The First Affiliated Hospital, Zhejiang University, Hangzhou, China. FAU - Chen, Sai-Juan AU - Chen SJ AD - State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital Affiliated to SJTU School of Medicine and Key Laboratory of Systems Biomedicine Ministry of Education, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University (SJTU), Shanghai, China. FAU - Jin, Jie AU - Jin J AD - Department of Hematology and Institute of Hematology, The First Affiliated Hospital, Zhejiang University, Hangzhou, China. AD - Key Laboratory of Hematopoietic Malignancies, Hangzhou, Zhejiang Province, People's Republic of China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150113 PL - United States TA - Int J Cancer JT - International journal of cancer JID - 0042124 RN - EC 1.1.1.41 (Isocitrate Dehydrogenase) RN - EC 1.1.1.41 (isocitrate dehydrogenase 2, human) RN - EC 1.1.1.42. (IDH1 protein, human) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Aged, 80 and over MH - Female MH - Gene Expression Profiling MH - Gene Expression Regulation, Leukemic MH - Humans MH - Isocitrate Dehydrogenase/*genetics MH - Karyotype MH - Leukemia, Myeloid, Acute/*genetics/*pathology MH - Male MH - Middle Aged MH - Mutation MH - Prognosis MH - Survival Analysis MH - *Up-Regulation MH - Young Adult OTO - NOTNLM OT - acute myeloid leukemia OT - gene expression OT - isocitrate dehydrogenase 1 OT - prognosis EDAT- 2014/12/20 06:00 MHDA- 2016/03/02 06:00 CRDT- 2014/12/20 06:00 PHST- 2014/05/21 [received] PHST- 2014/12/04 [accepted] PHST- 2015/01/13 [aheadofprint] AID - 10.1002/ijc.29395 [doi] PST - ppublish SO - Int J Cancer. 2015 Sep 1;137(5):1058-65. doi: 10.1002/ijc.29395. Epub 2015 Jan 13. PMID- 25343280 OWN - NLM STAT- MEDLINE DA - 20150618 DCOM- 20160309 IS - 1607-8454 (Electronic) IS - 1024-5332 (Linking) VI - 20 IP - 6 DP - 2015 Jul TI - Integrating GO and KEGG terms to characterize and predict acute myeloid leukemia-related genes. PG - 336-42 LID - 10.1179/1607845414Y.0000000209 [doi] AB - BACKGROUND/OBJECTIVE: Acute myeloid leukemia (AML) is a progressive and malignant cancer of myelogenous blood cells, which disturbs the production of normal blood cells. Although several risk and genetic factors (AML-related genes) have been investigated, the concrete mechanism underlying the development of AML remains unclear. In view of this, it is crucial to develop an effective computational method for meaningfully characterizing AML genes and accurately predicting novel AML genes. METHODS: In this study, we integrated gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotations as features to characterize AML genes. We also provided an optimal set of features for predicting AML-related genes by using the minimum redundancy maximum relevance (mRMR) algorithm and dagging metaclassifier. RESULTS: We obtained 26 optimal GO terms that characterized AML genes well. Finally, we predicted 464 novel genes to provide clinical researchers with additional candidates and useful insights for further analysis of AML. DISCUSSION: An in-depth feature analysis indicated that the results are quite consistent with previous knowledge. We developed a systematic method to identify the possible underlying mechanism of AML by analyzing the related genes. Our method has the ability to identify the types of features that are optimal to meaningfully interpret AML and accurately predict more AML genes for further clinical researches. FAU - Chen, Jing AU - Chen J FAU - Li, Chao AU - Li C FAU - Zhu, Yingchao AU - Zhu Y FAU - Sun, Ling AU - Sun L FAU - Sun, Hui AU - Sun H FAU - Liu, Yanfang AU - Liu Y FAU - Zhang, Zhenxiang AU - Zhang Z FAU - Wang, Chong AU - Wang C LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20141024 PL - England TA - Hematology JT - Hematology (Amsterdam, Netherlands) JID - 9708388 SB - IM MH - Computational Biology MH - *Gene Ontology MH - Humans MH - Leukemia, Myeloid, Acute/*genetics MH - Molecular Sequence Annotation/*methods OTO - NOTNLM OT - AML-related genes OT - Gene ontology OT - KEGG pathway OT - Prediction of AML genes EDAT- 2014/10/25 06:00 MHDA- 2016/03/10 06:00 CRDT- 2014/10/25 06:00 PHST- 2014/10/24 [aheadofprint] AID - 10.1179/1607845414Y.0000000209 [doi] PST - ppublish SO - Hematology. 2015 Jul;20(6):336-42. doi: 10.1179/1607845414Y.0000000209. Epub 2014 Oct 24. PMID- 25248882 OWN - NLM STAT- MEDLINE DA - 20150619 DCOM- 20160325 IS - 1029-2403 (Electronic) IS - 1026-8022 (Linking) VI - 56 IP - 5 DP - 2015 May TI - A Phase 1 study of the safety, pharmacokinetics and anti-leukemic activity of the anti-CD123 monoclonal antibody CSL360 in relapsed, refractory or high-risk acute myeloid leukemia. PG - 1406-15 LID - 10.3109/10428194.2014.956316 [doi] AB - Acute myeloid leukemia (AML) blasts express high levels of interlekin-3 (IL-3) receptor-alpha (CD123). CSL360 is a recombinant, chimeric immunoglobulin G1 (IgG1), anti-CD123 monoclonal antibody (MoAb) that neutralizes IL-3 and demonstrates anti-leukemic activity in vitro. This phase 1 study assessed safety, pharmacokinetics and bioactivity of weekly intravenous CSL360 for 12 weeks in 40 patients with advanced AML across five dose levels (0.1-10.0 mg/kg). Other than mild infusion reactions, CSL360 was well tolerated. The maximal tolerated dose was not reached. The half-life was 4.9 days, and the area under the curve (AUC) and maximum concentration (Cmax) increased proportionally with dose. Doses >/= 3.0 mg/kg resulted in complete saturation and down-regulation of CD123 and abolition of ex vivo proliferative responsiveness to IL-3, indicating adequate blockade of IL-3 signaling. Two patients responded, with one remaining in complete remission after 17 doses. CSL360 bound CD123 specifically, but did not induce anti-leukemic activity in most patients. While safe, MoAb blockade of CD123 function is insufficient as a therapeutic strategy. FAU - He, Simon Z AU - He SZ AD - Department of Clinical Haematology and BMT Service, The Royal Melbourne Hospital , Melbourne , Australia. FAU - Busfield, Samantha AU - Busfield S FAU - Ritchie, David S AU - Ritchie DS FAU - Hertzberg, Mark S AU - Hertzberg MS FAU - Durrant, Simon AU - Durrant S FAU - Lewis, Ian D AU - Lewis ID FAU - Marlton, Paula AU - Marlton P FAU - McLachlan, Andrew J AU - McLachlan AJ FAU - Kerridge, Ian AU - Kerridge I FAU - Bradstock, Kenneth F AU - Bradstock KF FAU - Kennedy, Glen AU - Kennedy G FAU - Boyd, Andrew W AU - Boyd AW FAU - Yeadon, Trina M AU - Yeadon TM FAU - Lopez, Angel F AU - Lopez AF FAU - Ramshaw, Hayley S AU - Ramshaw HS FAU - Iland, Harry AU - Iland H FAU - Bamford, Simone AU - Bamford S FAU - Barnden, Megan AU - Barnden M FAU - DeWitte, Mark AU - DeWitte M FAU - Basser, Russell AU - Basser R FAU - Roberts, Andrew W AU - Roberts AW LA - eng PT - Clinical Trial, Phase I PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20141120 PL - England TA - Leuk Lymphoma JT - Leukemia & lymphoma JID - 9007422 RN - 0 (Antibodies, Monoclonal) RN - 0 (Antineoplastic Agents) RN - 0 (CSL360) RN - 0 (Interleukin-3) RN - 0 (Interleukin-3 Receptor alpha Subunit) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Antibodies, Monoclonal/administration & dosage/adverse effects/pharmacokinetics/*therapeutic use MH - Antineoplastic Agents/administration & dosage/adverse effects/pharmacokinetics/*therapeutic use MH - Cell Proliferation/drug effects MH - Female MH - Gene Expression Regulation, Leukemic MH - Humans MH - Interleukin-3/metabolism MH - Interleukin-3 Receptor alpha Subunit/antagonists & inhibitors/genetics/metabolism MH - Leukemia, Myeloid, Acute/*drug therapy/*pathology MH - Male MH - Middle Aged MH - Recurrence MH - Treatment Outcome MH - Young Adult OTO - NOTNLM OT - Acute myeloid leukemia (AML) OT - immunotherapy OT - interleukin-3 (IL-3) receptor-alpha (CD123) OT - leukemic stem cell (LSC) EDAT- 2014/09/25 06:00 MHDA- 2016/03/26 06:00 CRDT- 2014/09/25 06:00 PHST- 2014/11/20 [aheadofprint] AID - 10.3109/10428194.2014.956316 [doi] PST - ppublish SO - Leuk Lymphoma. 2015 May;56(5):1406-15. doi: 10.3109/10428194.2014.956316. Epub 2014 Nov 20. PMID- 25248875 OWN - NLM STAT- MEDLINE DA - 20150619 DCOM- 20160325 IS - 1029-2403 (Electronic) IS - 1026-8022 (Linking) VI - 56 IP - 5 DP - 2015 May TI - Expression of indoleamine 2,3-dioxygenase in leukemic cells indicates an unfavorable prognosis in acute myeloid leukemia patients with intermediate-risk cytogenetics. PG - 1398-405 LID - 10.3109/10428194.2014.953150 [doi] AB - The immunomodulatory effects of indoleamine 2,3-dioxygenase (IDO) are ascribed to its ability to catalyze breakdown of the essential amino acid L-tryptophan. We applied reverse transcription-polymerase chain reaction (RT-PCR) to examine IDO mRNA expression in acute myeloid leukemia (AML) blasts, and investigated its clinical significance. We enrolled 62 patients with AML between April 2005 and March 2013. Bone marrow-derived mononuclear fractions were separated and extracted mRNA was amplified by PCR. RT-PCR showed that the bone marrow of 23 patients expressed IDO mRNA but not in 39. IDO mRNA expression did not significantly differ among cytogenetic risk profiles. The 3-year overall survival rates for patients with and without IDO mRNA expression were 39% and 74%, respectively (p < 0.005). The rates for patients with intermediate-risk cytogenetics with and without IDO mRNA expression were 16% and 70%, respectively (p < 0.005). The expression of IDO mRNA was associated with a poor prognosis of AML. FAU - Fukuno, Kenji AU - Fukuno K AD - First Department of Internal Medicine. FAU - Hara, Takeshi AU - Hara T FAU - Tsurumi, Hisashi AU - Tsurumi H FAU - Shibata, Yuhei AU - Shibata Y FAU - Mabuchi, Ryoko AU - Mabuchi R FAU - Nakamura, Nobuhiko AU - Nakamura N FAU - Kitagawa, Junichi AU - Kitagawa J FAU - Shimizu, Masahito AU - Shimizu M FAU - Ito, Hiroyasu AU - Ito H FAU - Saito, Kuniaki AU - Saito K FAU - Moriwaki, Hisataka AU - Moriwaki H LA - eng PT - Journal Article DEP - 20141103 PL - England TA - Leuk Lymphoma JT - Leukemia & lymphoma JID - 9007422 RN - 0 (Biomarkers) RN - 0 (Indoleamine-Pyrrole 2,3,-Dioxygenase) RN - EC 2.7.10.1 (FLT3 protein, human) RN - EC 2.7.10.1 (fms-Like Tyrosine Kinase 3) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Aged, 80 and over MH - Biomarkers MH - *Chromosome Aberrations MH - Female MH - Gene Duplication MH - *Gene Expression Regulation, Leukemic MH - *Genetic Predisposition to Disease MH - Humans MH - Immunophenotyping MH - Indoleamine-Pyrrole 2,3,-Dioxygenase/*genetics MH - Leukemia, Myeloid, Acute/diagnosis/*genetics/*mortality MH - Male MH - Middle Aged MH - Prognosis MH - Tandem Repeat Sequences MH - Young Adult MH - fms-Like Tyrosine Kinase 3/genetics OTO - NOTNLM OT - Immunological tolerance OT - acute myeloid leukemia OT - indoleamine 2,3-dioxygenase OT - l-tryptophan catabolism OT - prognostic factor EDAT- 2014/09/25 06:00 MHDA- 2016/03/26 06:00 CRDT- 2014/09/25 06:00 PHST- 2014/11/03 [aheadofprint] AID - 10.3109/10428194.2014.953150 [doi] PST - ppublish SO - Leuk Lymphoma. 2015 May;56(5):1398-405. doi: 10.3109/10428194.2014.953150. Epub 2014 Nov 3. PMID- 25242094 OWN - NLM STAT- MEDLINE DA - 20150619 DCOM- 20160325 IS - 1029-2403 (Electronic) IS - 1026-8022 (Linking) VI - 56 IP - 5 DP - 2015 May TI - MicroRNAs expressed in hematopoietic stem/progenitor cells are deregulated in acute myeloid leukemias. PG - 1466-74 LID - 10.3109/10428194.2014.955019 [doi] AB - MicroRNAs are key regulators of hematopoiesis, specifically involved in regulating the maintenance of stemness of primitive hematopoietic progenitor cells (HPCs) and the early and late stages of hematopoietic differentiation. Some microRNAs have been found to be expressed in hematopoietic stem cells (HSCs) and primitive HPCs, and play a relevant role in regulation of the early steps of hematopoietic cell differentiation. Notable examples of these microRNAs are given by miR-22, miR-29, miR-125 and miR-126. These HSC/HPC-regulating microRNAs are often deregulated in some subsets of acute myeloid leukemia (AML), with pathogenic, diagnostic and prognostic implications. Therefore, elucidation of the pattern of microRNA expression at the level of the early stages of hematopoietic cell differentiation has essential implications, not only for elucidation of the molecular bases of the early stages of hematopoietic differentiation, but also for a better understanding of the pathogenic mechanisms underlying AML. FAU - Testa, Ugo AU - Testa U AD - Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanita , Rome , Italy. FAU - Pelosi, Elvira AU - Pelosi E LA - eng PT - Journal Article PT - Review DEP - 20150121 PL - England TA - Leuk Lymphoma JT - Leukemia & lymphoma JID - 9007422 RN - 0 (MicroRNAs) SB - IM MH - Cell Transformation, Neoplastic/genetics MH - *Gene Expression Regulation, Leukemic MH - Hematopoiesis MH - Hematopoietic Stem Cells/*metabolism MH - Humans MH - Leukemia, Myeloid, Acute/*genetics MH - MicroRNAs/*genetics MH - RNA Interference OTO - NOTNLM OT - Basic biology OT - myeloid leukemias and dysplasias OT - stem and primitive progenitor cells EDAT- 2014/09/23 06:00 MHDA- 2016/03/26 06:00 CRDT- 2014/09/23 06:00 PHST- 2015/01/21 [aheadofprint] AID - 10.3109/10428194.2014.955019 [doi] PST - ppublish SO - Leuk Lymphoma. 2015 May;56(5):1466-74. doi: 10.3109/10428194.2014.955019. Epub 2015 Jan 21. PMID- 25232917 OWN - NLM STAT- MEDLINE DA - 20150618 DCOM- 20160309 IS - 1607-8454 (Electronic) IS - 1024-5332 (Linking) VI - 20 IP - 6 DP - 2015 Jul TI - Clinical impact of SNP of P53 genes pathway on the adult AML patients. PG - 328-35 LID - 10.1179/1607845414Y.0000000200 [doi] AB - INTRODUCTION: Acute myeloid leukemia (AML) is a highly heterogeneous disease, with biologically and prognostically different subtypes. AIM: To study the impact of p53, p21, and mdm2 gene polymorphisms on the clinical outcome in adult AML patients treated at the National Cancer Institute (NCI) - Cairo University. METHODS: Forty-eight adult AML patients presented to the Medical Oncology Department, NCI, from April 2010 till November 2011. Clinical data and bone marrow samples were obtained. Molecular genetic analysis involving P53, MDM2, and P21 single-nucleotide gene polymorphisms was done using polymerase chain reaction-restriction fragment length polymorphism coupled analysis. RESULTS: The mean age was 35.7 years. After a median follow-up period of 12 months, 28 patients (58.4%) achieved complete remission (CR) and the overall survival (OS) was 8.7 months. Patients with homozygous Arg/arg at codon 72 of P53 had a better median OS months than Arg/Pro and Pro/Pro (13.4 vs. 8.4 vs. 1.5 months, respectively; P = 0.045). P53/p21 combination had a better median OS and disease-free survival (DFS) of 12.1 and 13.7 months for wild type cases (GG + Ser/ser) and 20.3 and 20.7 months for patients with either variant genes (GC + Ser/arg) compared with 1.1 and 1.9 months for patients with both variant genes (CC + arg/arg), (P = 0.037 and 0.004). The presence of wild genotype of either P21 or MDM2 may abolish the effect of P53 homozygous variant genotype on the OS. Neither p21nor mdm2 polymorphism alone showed an impact on OS or DFS. CR was not affected by any of the three gene polymorphisms. CONCLUSION: The p53 pathway gene polymorphisms may affect the OS of adult AML patients. FAU - Abdel Hamid, Thoraya M AU - Abdel Hamid TM FAU - El Gammal, Mosaad M AU - El Gammal MM FAU - Eibead, Gamal T AU - Eibead GT FAU - Saber, Mostafa M AU - Saber MM FAU - Abol Elazm, Omnia M AU - Abol Elazm OM LA - eng PT - Journal Article DEP - 20140918 PL - England TA - Hematology JT - Hematology (Amsterdam, Netherlands) JID - 9708388 SB - IM MH - Adolescent MH - Adult MH - Disease-Free Survival MH - Female MH - Genes, p53 MH - Genetic Predisposition to Disease MH - Genotyping Techniques MH - Humans MH - Leukemia, Myeloid, Acute/*genetics MH - Male MH - Middle Aged MH - Polymorphism, Single Nucleotide/*genetics MH - Retrospective Studies MH - Treatment Outcome MH - Young Adult OTO - NOTNLM OT - Acute myeloid leukemia OT - Clinical outcome OT - Polymorphism OT - mdm2 OT - p21 OT - p53 gene EDAT- 2014/09/19 06:00 MHDA- 2016/03/10 06:00 CRDT- 2014/09/19 06:00 PHST- 2014/09/18 [aheadofprint] AID - 10.1179/1607845414Y.0000000200 [doi] PST - ppublish SO - Hematology. 2015 Jul;20(6):328-35. doi: 10.1179/1607845414Y.0000000200. Epub 2014 Sep 18. PMID- 25204372 OWN - NLM STAT- MEDLINE DA - 20150619 DCOM- 20160325 IS - 1029-2403 (Electronic) IS - 1026-8022 (Linking) VI - 56 IP - 5 DP - 2015 May TI - Impact of pre-transplant disease burden on the outcome of allogeneic hematopoietic stem cell transplant in refractory and relapsed acute myeloid leukemia: a single-center study. PG - 1353-61 LID - 10.3109/10428194.2014.961016 [doi] AB - Patients with refractory or relapsed acute myeloid leukemia (AML) receiving allogeneic hematopoietic stem cell transplant (HSCT) were retrospectively assessed to evaluate the effect of disease burden on outcomes and to identify predictive variables. Of all patients, 53 achieved a complete morphological remission (CR-AML) before transplant, while 48 failed to do so (NR-AML). In the CR-AML group, 32 patients displayed minimal residual disease (MRDpos). Estimated 5-year overall survival (5-OS) and disease-free survival of all patients was 37% and 29%, respectively. The 5-OS was significantly different between patients with CR-AML and NR-AML (46% vs. 18%). However, pre-transplant MRD status did not affect 5-OS (51% in MRDneg vs. 41% in MRDpos). Using multivariate analysis, we identified patient's physical condition and risk stratification as additional prognostic factors. Our findings suggest that NR status influences the outcomes of HSCT while pre-transplant MRD does not. HSCT needs to be optimized accordingly to treat high risk AML. FAU - Tian, Hong AU - Tian H AD - Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, The First A liated Hospital of Soochow University , Suzhou , China. FAU - Chen, Guang-Hua AU - Chen GH FAU - Xu, Yang AU - Xu Y FAU - Ma, Xiao AU - Ma X FAU - Chen, Feng AU - Chen F FAU - Yang, Zhen AU - Yang Z FAU - Jin, Zheng-Ming AU - Jin ZM FAU - Qiu, Hui-Ying AU - Qiu HY FAU - Sun, Ai-Ning AU - Sun AN FAU - Wu, De-Pei AU - Wu DP LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20141009 PL - England TA - Leuk Lymphoma JT - Leukemia & lymphoma JID - 9007422 SB - IM MH - Adolescent MH - Adult MH - Child MH - Child, Preschool MH - Disease Progression MH - Female MH - Graft vs Host Disease/etiology MH - *Hematopoietic Stem Cell Transplantation/adverse effects MH - Humans MH - Leukemia, Myeloid, Acute/diagnosis/mortality/*pathology MH - Male MH - Middle Aged MH - Neoplasm, Residual MH - Prognosis MH - Recurrence MH - Retrospective Studies MH - Survival Analysis MH - Transplantation, Homologous MH - Treatment Outcome MH - Tumor Burden MH - Young Adult OTO - NOTNLM OT - Acute myeloid leukemia OT - allogeneic hematopoietic stem cell transplant OT - minimal residual disease OT - refractory OT - relapse EDAT- 2014/09/11 06:00 MHDA- 2016/03/26 06:00 CRDT- 2014/09/11 06:00 PHST- 2014/10/09 [aheadofprint] AID - 10.3109/10428194.2014.961016 [doi] PST - ppublish SO - Leuk Lymphoma. 2015 May;56(5):1353-61. doi: 10.3109/10428194.2014.961016. Epub 2014 Oct 9. PMID- 25110819 OWN - NLM STAT- MEDLINE DA - 20150619 DCOM- 20160325 LR - 20150620 IS - 1029-2403 (Electronic) IS - 1026-8022 (Linking) VI - 56 IP - 5 DP - 2015 May TI - Incidence of and risk factors for involvement of the central nervous system in acute myeloid leukemia. PG - 1392-7 LID - 10.3109/10428194.2014.953148 [doi] AB - It is thought that the low incidence of central nervous system (CNS) involvement in acute myeloid leukemia (AML) does not justify routine CNS prophylaxis, as high-dose cytarabine eliminates CNS disease. To investigate whether chemotherapy that does not include high-dose cytarabine increases the risk of CNS involvement, the medical records of 1412 newly diagnosed patients with AML were reviewed. In 1370 patients, lumbar puncture (LP) was performed only if clinically indicated, and CNS disease was detected in 45 (3.3%) patients. Another 42 patients underwent routine LP as part of an investigational protocol, and in eight (19%) CNS disease was detected (p < 0.0001). Risk factors included high lactate dehydrogenase, African-American ethnicity and young age. Patients receiving high-dose cytarabine and those who did not had similar rates of CNS involvement. Disease-free survival (DFS) and overall survival were shorter in patients with CNS involvement. It remains to be determined whether routine CNS prophylaxis would improve DFS. FAU - Rozovski, Uri AU - Rozovski U AD - Department of Leukemia, The University of Texas M. D. Anderson Cancer Center , Houston, TX , USA. FAU - Ohanian, Maro AU - Ohanian M FAU - Ravandi, Farhad AU - Ravandi F FAU - Garcia-Manero, Guillermo AU - Garcia-Manero G FAU - Faderl, Stefan AU - Faderl S FAU - Pierce, Sherry AU - Pierce S FAU - Cortes, Jorge AU - Cortes J FAU - Estrov, Zeev AU - Estrov Z LA - eng GR - P30 CA016672/CA/NCI NIH HHS/United States GR - P30 CA016672/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20141103 PL - England TA - Leuk Lymphoma JT - Leukemia & lymphoma JID - 9007422 RN - 04079A1RDZ (Cytarabine) SB - IM CIN - Leuk Lymphoma. 2015 Jul;56(7):2190-2. PMID: 25641427 MH - Adolescent MH - Adult MH - Aged MH - Aged, 80 and over MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects/therapeutic use MH - Central Nervous System Neoplasms/diagnosis/*epidemiology/*secondary MH - Cytarabine/administration & dosage MH - Female MH - Humans MH - Incidence MH - Leukemia, Myeloid, Acute/*complications/*epidemiology MH - Male MH - Middle Aged MH - Odds Ratio MH - Prognosis MH - Risk Factors MH - Survival Analysis MH - Young Adult PMC - PMC4417664 MID - NIHMS629662 OID - NLM: NIHMS629662 OID - NLM: PMC4417664 OTO - NOTNLM OT - Acute myeloid leukemia OT - central nervous system OT - cytarabine OT - lumbar puncture OT - risk factors EDAT- 2014/08/12 06:00 MHDA- 2016/03/26 06:00 CRDT- 2014/08/12 06:00 PHST- 2014/11/03 [aheadofprint] AID - 10.3109/10428194.2014.953148 [doi] PST - ppublish SO - Leuk Lymphoma. 2015 May;56(5):1392-7. doi: 10.3109/10428194.2014.953148. Epub 2014 Nov 3. PMID- 24884314 OWN - NLM STAT- MEDLINE DA - 20150311 DCOM- 20160322 IS - 1029-2403 (Electronic) IS - 1026-8022 (Linking) VI - 56 IP - 3 DP - 2015 Mar TI - Higher percentage of CD34 + CD38- cells detected by multiparameter flow cytometry from leukapheresis products predicts unsustained complete remission in acute myeloid leukemia. PG - 622-9 LID - 10.3109/10428194.2014.927453 [doi] AB - Relapse in acute myeloid leukemia (AML) after chemotherapy reflects the persistence of resistant leukemia stem cells (LSCs). These cells have been described in the CD34 + CD38- cell fraction. Leukapheresis products were harvested in 123 patients in morphological complete remission and analyzed by multiparameter flow cytometry. The CD34 + CD38- cell population showed a prognostic impact on survival. Median event-free survival (EFS) was 8.2 months (3-year EFS: 29%) for those with a higher percentage of CD34 + CD38- versus 91.9 months (3-year EFS: 62%) for those with a lower percentage for the entire cohort. These differences were confirmed in patients undergoing autologous stem cell transplant, with median EFS of 7.3 months versus 91.1 months (3-year EFS: 31% vs. 70%). Higher proportions of CD34 + CD38- cells were associated with adverse cytogenetics and with earlier relapses. Higher percentages of CD34 + CD38- cells in apheresis products reflect inadequate in vivo purging and reliably distinguish samples enriched in LSCs from those involving mainly normal cells. FAU - Plesa, Adriana AU - Plesa A AD - Laboratory of Hematology. FAU - Elhamri, Mohamed AU - Elhamri M FAU - Clapisson, Gilles AU - Clapisson G FAU - Mattei, Eve AU - Mattei E FAU - Gazzo, Sophie AU - Gazzo S FAU - Hequet, Olivier AU - Hequet O FAU - Tigaud, Isabelle AU - Tigaud I FAU - Michallet, Mauricette AU - Michallet M FAU - Dumontet, Charles AU - Dumontet C FAU - Thomas, Xavier AU - Thomas X LA - eng PT - Journal Article DEP - 20140717 PL - England TA - Leuk Lymphoma JT - Leukemia & lymphoma JID - 9007422 RN - 0 (Antigens, CD34) RN - EC 3.2.2.5 (Antigens, CD38) SB - IM MH - Adult MH - Aged MH - Antigens, CD34/*blood MH - Antigens, CD38/*blood MH - Disease-Free Survival MH - *Flow Cytometry MH - Humans MH - Leukapheresis/*methods MH - Leukemia, Myeloid, Acute/*diagnosis/mortality MH - Middle Aged MH - Neoplastic Stem Cells/cytology MH - Recurrence OTO - NOTNLM OT - Acute myeloid leukemia OT - autologous transplant OT - leukemia stem cell OT - prognosis OT - stem cell harvest EDAT- 2014/06/03 06:00 MHDA- 2016/03/24 06:00 CRDT- 2014/06/03 06:00 PHST- 2014/07/17 [aheadofprint] AID - 10.3109/10428194.2014.927453 [doi] PST - ppublish SO - Leuk Lymphoma. 2015 Mar;56(3):622-9. doi: 10.3109/10428194.2014.927453. Epub 2014 Jul 17. PMID- 24882254 OWN - NLM STAT- MEDLINE DA - 20150311 DCOM- 20160314 IS - 1029-2403 (Electronic) IS - 1026-8022 (Linking) VI - 56 IP - 3 DP - 2015 Mar TI - Factors associated with early reinduction chemotherapy for adults with acute myeloid leukemia. PG - 782-4 LID - 10.3109/10428194.2014.928931 [doi] FAU - Ueda, Masumi AU - Ueda M AD - Department of Medicine, University of Washington , Seattle, WA , USA. FAU - Xie, Hu AU - Xie H FAU - Sandhu, Ravinder K AU - Sandhu RK FAU - Walter, Roland B AU - Walter RB FAU - Pagel, John M AU - Pagel JM FAU - Estey, Elihu H AU - Estey EH LA - eng PT - Letter DEP - 20140717 PL - England TA - Leuk Lymphoma JT - Leukemia & lymphoma JID - 9007422 RN - 04079A1RDZ (Cytarabine) SB - IM MH - Acute Disease MH - Adult MH - Aged MH - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use MH - Bone Marrow Examination MH - Cell Count MH - Cytarabine/administration & dosage/*therapeutic use MH - Humans MH - Induction Chemotherapy/*methods MH - Leukemia, Myeloid/*drug therapy/pathology MH - Middle Aged MH - Neoplastic Stem Cells/drug effects/pathology MH - Remission Induction MH - Retreatment MH - Time Factors EDAT- 2014/06/03 06:00 MHDA- 2016/03/15 06:00 CRDT- 2014/06/03 06:00 PHST- 2014/07/17 [aheadofprint] AID - 10.3109/10428194.2014.928931 [doi] PST - ppublish SO - Leuk Lymphoma. 2015 Mar;56(3):782-4. doi: 10.3109/10428194.2014.928931. Epub 2014 Jul 17. PMID- 24313832 OWN - NLM STAT- MEDLINE DA - 20140625 DCOM- 20160322 IS - 1029-2403 (Electronic) IS - 1026-8022 (Linking) VI - 55 IP - 7 DP - 2014 Jul TI - Prognostic significance of additional cytogenetic abnormalities and FLT3 mutations in acute promyelocytic leukemia. PG - 1444-6 LID - 10.3109/10428194.2013.868458 [doi] FAU - Dillon, Richard AU - Dillon R AD - Department of Medical and Molecular Genetics, King's College London School of Medicine , London , UK. FAU - Grimwade, David AU - Grimwade D LA - eng PT - Comment PT - Journal Article DEP - 20140128 PL - England TA - Leuk Lymphoma JT - Leukemia & lymphoma JID - 9007422 RN - 0 (Antineoplastic Agents) RN - 0 (Arsenicals) RN - 0 (Oxides) RN - EC 2.7.10.1 (fms-Like Tyrosine Kinase 3) RN - S7V92P67HO (arsenic trioxide) SB - IM CON - Leuk Lymphoma. 2014 Jul;55(7):1523-32. PMID: 24160850 MH - Antineoplastic Agents/*therapeutic use MH - Arsenicals/*therapeutic use MH - Female MH - Humans MH - *Karyotype MH - Leukemia, Promyelocytic, Acute/*drug therapy/*genetics MH - Male MH - *Mutation MH - Oxides/*therapeutic use MH - fms-Like Tyrosine Kinase 3/*genetics EDAT- 2013/12/10 06:00 MHDA- 2016/03/24 06:00 CRDT- 2013/12/10 06:00 PHST- 2014/01/28 [aheadofprint] AID - 10.3109/10428194.2013.868458 [doi] PST - ppublish SO - Leuk Lymphoma. 2014 Jul;55(7):1444-6. doi: 10.3109/10428194.2013.868458. Epub 2014 Jan 28. PMID- 24206095 OWN - NLM STAT- MEDLINE DA - 20140625 DCOM- 20160322 IS - 1029-2403 (Electronic) IS - 1026-8022 (Linking) VI - 55 IP - 7 DP - 2014 Jul TI - Letting microRNAs overcome resistance to chemotherapy in acute myeloid leukemia. PG - 1449-50 LID - 10.3109/10428194.2013.862244 [doi] FAU - Sakamoto, Kathleen M AU - Sakamoto KM AD - Division of Hematology/Oncology, Department of Pediatrics, Stanford University School of Medicine , Stanford, CA , USA. LA - eng PT - Comment PT - Journal Article DEP - 20140128 PL - England TA - Leuk Lymphoma JT - Leukemia & lymphoma JID - 9007422 RN - 0 (MIRN7 microRNA, human) RN - 0 (MicroRNAs) SB - IM CON - Leuk Lymphoma. 2014 Jul;55(7):1645-8. PMID: 24067109 MH - Drug Resistance, Neoplasm/*genetics MH - *Gene Expression Regulation, Leukemic MH - Humans MH - Leukemia, Myeloid, Acute/*genetics MH - MicroRNAs/*genetics EDAT- 2013/11/12 06:00 MHDA- 2016/03/24 06:00 CRDT- 2013/11/12 06:00 PHST- 2014/01/28 [aheadofprint] AID - 10.3109/10428194.2013.862244 [doi] PST - ppublish SO - Leuk Lymphoma. 2014 Jul;55(7):1449-50. doi: 10.3109/10428194.2013.862244. Epub 2014 Jan 28. PMID- 24160850 OWN - NLM STAT- MEDLINE DA - 20140625 DCOM- 20160322 LR - 20151217 IS - 1029-2403 (Electronic) IS - 1026-8022 (Linking) VI - 55 IP - 7 DP - 2014 Jul TI - Arsenic trioxide in front-line therapy of acute promyelocytic leukemia (C9710): prognostic significance of FLT3 mutations and complex karyotype. PG - 1523-32 LID - 10.3109/10428194.2013.842985 [doi] AB - The addition of arsenic trioxide (ATO) to frontline therapy of acute promyelocytic leukemia (APL) has been shown to result in significant improvements in disease-free survival (DFS). FLT3 mutations are frequently observed in APL, but its prognostic significance remains unclear. We analyzed 245 newly diagnosed adult patients with APL treated on intergroup trial C9710 and evaluated previously defined biological and prognostic factors and their relationship to FLT3 mutations and to additional karyotypic abnormalities. FLT3 mutations were found in 48% of patients, including 31% with an internal tandem duplication (FLT3-ITD), 14% with a point mutation (FLT3-D835) and 2% with both mutations. The FLT3-ITD mutant level was uniformly low, < 0.5. Neither FLT3 mutation had an impact on remission rate, induction death rate, DFS or overall survival (OS). The addition of ATO consolidation improved outcomes regardless of FLT3 mutation type or level, initial white blood cell count, PML-RARA isoform type or transcript level. The presence of a complex karyotype was strongly associated with an inferior OS independently of post-remission treatment. In conclusion, the addition of ATO to frontline therapy overcomes the impact of previously described adverse prognostic factors including FLT3 mutations. However, complex karyotype is strongly associated with an inferior OS despite ATO therapy. FAU - Poire, Xavier AU - Poire X AD - Section of Hematology/Oncology, The University of Chicago Medical Center , Chicago, IL , USA. FAU - Moser, Barry K AU - Moser BK FAU - Gallagher, Robert E AU - Gallagher RE FAU - Laumann, Kristina AU - Laumann K FAU - Bloomfield, Clara D AU - Bloomfield CD FAU - Powell, Bayard L AU - Powell BL FAU - Koval, Gregory AU - Koval G FAU - Gulati, Kabir AU - Gulati K FAU - Holowka, Nicholas AU - Holowka N FAU - Larson, Richard A AU - Larson RA FAU - Tallman, Martin S AU - Tallman MS FAU - Appelbaum, Frederick R AU - Appelbaum FR FAU - Sher, Dorie AU - Sher D FAU - Willman, Cheryl AU - Willman C FAU - Paietta, Elisabeth AU - Paietta E FAU - Stock, Wendy AU - Stock W LA - eng GR - CA021115/CA/NCI NIH HHS/United States GR - CA114737/CA/NCI NIH HHS/United States GR - CA31946/CA/NCI NIH HHS/United States GR - CA56771/CA/NCI NIH HHS/United States GR - U10 CA031946/CA/NCI NIH HHS/United States GR - U10 CA037403/CA/NCI NIH HHS/United States GR - U10 CA180820/CA/NCI NIH HHS/United States GR - U10 CA180861/CA/NCI NIH HHS/United States GR - U10 CA180888/CA/NCI NIH HHS/United States GR - U24 CA114737/CA/NCI NIH HHS/United States PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20140204 PL - England TA - Leuk Lymphoma JT - Leukemia & lymphoma JID - 9007422 RN - 0 (Antineoplastic Agents) RN - 0 (Arsenicals) RN - 0 (Oncogene Proteins, Fusion) RN - 0 (Oxides) RN - 0 (promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein) RN - EC 2.7.10.1 (fms-Like Tyrosine Kinase 3) RN - S7V92P67HO (arsenic trioxide) SB - IM CIN - Leuk Lymphoma. 2014 Jul;55(7):1444-6. PMID: 24313832 MH - Adolescent MH - Adult MH - Aged MH - Aged, 80 and over MH - Antineoplastic Agents/*therapeutic use MH - Arsenicals/*therapeutic use MH - Bone Marrow/pathology MH - Female MH - Humans MH - *Karyotype MH - Leukemia, Promyelocytic, Acute/diagnosis/*drug therapy/*genetics/mortality MH - Male MH - Middle Aged MH - *Mutation MH - Oncogene Proteins, Fusion/genetics MH - Oxides/*therapeutic use MH - Prognosis MH - Treatment Outcome MH - Young Adult MH - fms-Like Tyrosine Kinase 3/*genetics PMC - PMC4273565 MID - NIHMS624152 OID - NLM: NIHMS624152 OID - NLM: PMC4273565 OTO - NOTNLM OT - Acute promyelocytic leukemia OT - FLT3 mutations OT - arsenic trioxide OT - complex karyotype OT - mutant level OT - prognosis EDAT- 2013/10/29 06:00 MHDA- 2016/03/24 06:00 CRDT- 2013/10/29 06:00 PHST- 2014/02/04 [aheadofprint] AID - 10.3109/10428194.2013.842985 [doi] PST - ppublish SO - Leuk Lymphoma. 2014 Jul;55(7):1523-32. doi: 10.3109/10428194.2013.842985. Epub 2014 Feb 4. PMID- 24144313 OWN - NLM STAT- MEDLINE DA - 20140625 DCOM- 20160322 IS - 1029-2403 (Electronic) IS - 1026-8022 (Linking) VI - 55 IP - 7 DP - 2014 Jul TI - Ten-day decitabine as initial therapy for newly diagnosed patients with acute myeloid leukemia unfit for intensive chemotherapy. PG - 1533-7 LID - 10.3109/10428194.2013.856425 [doi] AB - We retrospectively reviewed outcomes in 45 previously untreated patients with acute myeloid leukemia (AML) considered unfit for chemotherapy who were treated with 10-day courses of decitabine 20 mg/m(2) daily outside of a clinical trial, with no cut-offs for organ function or performance status (PS). Nineteen had Eastern Cooperative Group performance status (ECOG PS) >/= 2, and 39 had >/= 2 comorbidities. Fourteen patients (31%) achieved complete remission (CR) and five (11%) CR with incomplete count recovery, for an overall response rate of 42%, after a median of 2 (range, 1-4) courses. The only pretreatment characteristic that differed significantly between responders and non-responders was percent marrow blasts (median 42% vs. 65%; p = 0.01). Median overall survival was 9.0 months; it was 19.4 and 2.3 months for responders and non-responders, respectively (p < 0.001). Thus 10-day decitabine therapy has efficacy in patients with AML considered unfit for chemotherapy, and may serve as a backbone for the addition of other novel agents. FAU - Bhatnagar, Bhavana AU - Bhatnagar B AD - University of Maryland Greenebaum Cancer Center , Baltimore MD , USA. FAU - Duong, Vu H AU - Duong VH FAU - Gourdin, Theodore S AU - Gourdin TS FAU - Tidwell, Michael L AU - Tidwell ML FAU - Chen, Ching AU - Chen C FAU - Ning, Yi AU - Ning Y FAU - Emadi, Ashkan AU - Emadi A FAU - Sausville, Edward A AU - Sausville EA FAU - Baer, Maria R AU - Baer MR LA - eng PT - Journal Article DEP - 20140204 PL - England TA - Leuk Lymphoma JT - Leukemia & lymphoma JID - 9007422 RN - 0 (Antimetabolites, Antineoplastic) RN - 776B62CQ27 (decitabine) RN - M801H13NRU (Azacitidine) SB - IM MH - Aged MH - Aged, 80 and over MH - Antimetabolites, Antineoplastic/administration & dosage/adverse effects/*therapeutic use MH - Azacitidine/administration & dosage/adverse effects/*analogs & derivatives/therapeutic use MH - Female MH - Humans MH - Leukemia, Myeloid, Acute/diagnosis/*drug therapy/mortality MH - Male MH - Middle Aged MH - Remission Induction MH - Retrospective Studies MH - Time Factors MH - Treatment Outcome OTO - NOTNLM OT - Decitabine OT - acute myeloid leukemia OT - demethylating agents OT - elderly EDAT- 2013/10/23 06:00 MHDA- 2016/03/24 06:00 CRDT- 2013/10/23 06:00 PHST- 2014/02/04 [aheadofprint] AID - 10.3109/10428194.2013.856425 [doi] PST - ppublish SO - Leuk Lymphoma. 2014 Jul;55(7):1533-7. doi: 10.3109/10428194.2013.856425. Epub 2014 Feb 4. PMID- 24090502 OWN - NLM STAT- MEDLINE DA - 20140625 DCOM- 20160322 IS - 1029-2403 (Electronic) IS - 1026-8022 (Linking) VI - 55 IP - 7 DP - 2014 Jul TI - Medium-sized FLT3 internal tandem duplications confer worse prognosis than short and long duplications in a non-elderly acute myeloid leukemia cohort. PG - 1510-7 LID - 10.3109/10428194.2013.850163 [doi] AB - Internal tandem duplications (ITDs) of the fms-like tyrosine kinase 3 (FLT3) gene occur in about 25% of patients with adult acute myeloid leukemia (AML). The aim of our study was to investigate the frequency of FLT3-ITD mutations followed by a detailed analysis of the mutational load and size of ITD insertions in a cohort consisting of 324 patients younger than 60 years old and treated with curative intention. FLT3-ITD alone did not influence overall survival (OS) or disease-free survival (DFS). We observed worse OS and DFS for patients with high mutational load indicative for loss of the FLT3 wild type allele (p = 0.010, p = 0.038, respectively). In multivariate analyses, patients with FLT3-ITD(48-60bp) showed worse OS and DFS compared to other groups (FLT3-ITD(neg), FLT3-ITD (< 48b), FLT3-ITD (> 60bp); p = 0.014, p = 0.019, respectively). Our novel observation suggested that not only high FLT3-ITD load, but also medium-sized ITD insertions (48-60 bp) represented an adverse prognostic subgroup of patients with AML. FAU - Koszarska, Magdalena AU - Koszarska M AD - Laboratory of Molecular Diagnostics, Hungarian National Blood Transfusion Service , Budapest , Hungary. FAU - Meggyesi, Nora AU - Meggyesi N FAU - Bors, Andras AU - Bors A FAU - Batai, Arpad AU - Batai A FAU - Csacsovszki, Otto AU - Csacsovszki O FAU - Lehoczky, Eniko AU - Lehoczky E FAU - Adam, Emma AU - Adam E FAU - Kozma, Andras AU - Kozma A FAU - Lovas, Nora AU - Lovas N FAU - Sipos, Andrea AU - Sipos A FAU - Krahling, Tunde AU - Krahling T FAU - Dolgos, Janos AU - Dolgos J FAU - Remenyi, Peter AU - Remenyi P FAU - Fekete, Sandor AU - Fekete S FAU - Masszi, Tamas AU - Masszi T FAU - Tordai, Attila AU - Tordai A FAU - Andrikovics, Hajnalka AU - Andrikovics H LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20131125 PL - England TA - Leuk Lymphoma JT - Leukemia & lymphoma JID - 9007422 RN - EC 2.7.10.1 (fms-Like Tyrosine Kinase 3) SB - IM MH - Adolescent MH - Adult MH - Antineoplastic Combined Chemotherapy Protocols/therapeutic use MH - Female MH - *Gene Duplication MH - Genotype MH - Hematopoietic Stem Cell Transplantation MH - Humans MH - Leukemia, Myeloid, Acute/diagnosis/*genetics/*mortality/therapy MH - Male MH - Middle Aged MH - Mutation MH - Prognosis MH - *Tandem Repeat Sequences MH - Treatment Outcome MH - Young Adult MH - fms-Like Tyrosine Kinase 3/*genetics OTO - NOTNLM OT - Acute myeloid leukemia OT - FLT3 internal tandem duplication OT - molecular genetics OT - mutation EDAT- 2013/10/05 06:00 MHDA- 2016/03/24 06:00 CRDT- 2013/10/05 06:00 PHST- 2013/11/25 [aheadofprint] AID - 10.3109/10428194.2013.850163 [doi] PST - ppublish SO - Leuk Lymphoma. 2014 Jul;55(7):1510-7. doi: 10.3109/10428194.2013.850163. Epub 2013 Nov 25. PMID- 24067109 OWN - NLM STAT- MEDLINE DA - 20140625 DCOM- 20160322 IS - 1029-2403 (Electronic) IS - 1026-8022 (Linking) VI - 55 IP - 7 DP - 2014 Jul TI - MicroRNA let-7f is down-regulated in patients with refractory acute myeloid leukemia and is involved in chemotherapy resistance of adriamycin-resistant leukemic cells. PG - 1645-8 LID - 10.3109/10428194.2013.847936 [doi] FAU - Dai, Chong-Wen AU - Dai CW AD - Department of Hematology, Institute of Molecular Hematology, The Second Xiangya Hospital, Central South University , Changsha, Hunan , China. FAU - Bai, Qing-Wei AU - Bai QW FAU - Zhang, Guang-Sen AU - Zhang GS FAU - Cao, Yi-Xiong AU - Cao YX FAU - Shen, Jian-Kai AU - Shen JK FAU - Pei, Min-Fei AU - Pei MF FAU - Yin, C Cameron AU - Yin CC LA - eng PT - Letter PT - Research Support, Non-U.S. Gov't DEP - 20131112 PL - England TA - Leuk Lymphoma JT - Leukemia & lymphoma JID - 9007422 RN - 0 (Antibiotics, Antineoplastic) RN - 0 (MIRN7 microRNA, human) RN - 0 (MicroRNAs) RN - 80168379AG (Doxorubicin) SB - IM CIN - Leuk Lymphoma. 2014 Jul;55(7):1449-50. PMID: 24206095 MH - Antibiotics, Antineoplastic/pharmacology/therapeutic use MH - Down-Regulation MH - Doxorubicin/pharmacology/therapeutic use MH - Drug Resistance, Neoplasm/*genetics MH - *Gene Expression Regulation, Leukemic MH - Humans MH - Leukemia, Myeloid, Acute/drug therapy/*genetics MH - MicroRNAs/*genetics EDAT- 2013/09/27 06:00 MHDA- 2016/03/24 06:00 CRDT- 2013/09/27 06:00 PHST- 2013/11/12 [aheadofprint] AID - 10.3109/10428194.2013.847936 [doi] PST - ppublish SO - Leuk Lymphoma. 2014 Jul;55(7):1645-8. doi: 10.3109/10428194.2013.847936. Epub 2013 Nov 12. PMID- 24047476 OWN - NLM STAT- MEDLINE DA - 20140625 DCOM- 20160322 IS - 1029-2403 (Electronic) IS - 1026-8022 (Linking) VI - 55 IP - 7 DP - 2014 Jul TI - The BCL2L10 Leu21Arg variant and risk of therapy-related myeloid neoplasms and de novo myelodysplastic syndromes. PG - 1538-43 LID - 10.3109/10428194.2013.845885 [doi] AB - Therapy-related myeloid neoplasms (t-MNs) are an increasingly recognized complication in patients previously treated with radiotherapy and/or chemotherapy for cancer or autoimmune disease. Single nucleotide variants (SNVs) in genes involved in the cellular pathways of detoxification, DNA repair and apoptosis may modify the individual risk of developing a t-MN. We studied the frequency of the SNVs of six genes involved in xenobiotic detoxification (CYP3A4, NQO1, GSTA1, GSTM1, GSTP1 and GSTT1), two DNA repair genes (RAD51 and XRCC3) and one key regulator of apoptosis (BCL2L10) in a case-control study including 111 cases of t-MN and 259 controls. This is the first report on the prevalence of BCL2L10 Leu21Arg polymorphism in myeloid malignancies. In this line, we also tested 146 cases of de novo myelodysplastic syndrome (MDS) and 109 cases of de novo acute myeloid leukemia (AML). Our results showed a significantly lower frequency of the BCL2L10-21Arg allele in patients with t-MN and de novo MDS compared to controls (Leu/Arg + Arg/Arg: 50.6% vs. 65.9%, p = 0.017 and 45.8% vs. 65.9%, p = 0.0003, respectively). Carriers of the BCL2L10-21Arg variant have a reduced risk of developing t-MN and de novo MDS. FAU - Fabiani, Emiliano AU - Fabiani E AD - Institute of Hematology, Universita Cattolica Sacro Cuore , Rome , Italy. FAU - Fianchi, Luana AU - Fianchi L FAU - Falconi, Giulia AU - Falconi G FAU - Boncompagni, Riccardo AU - Boncompagni R FAU - Criscuolo, Marianna AU - Criscuolo M FAU - Guidi, Francesco AU - Guidi F FAU - La Brocca, Antonella AU - La Brocca A FAU - Hohaus, Stefan AU - Hohaus S FAU - Leone, Giuseppe AU - Leone G FAU - Voso, Maria Teresa AU - Voso MT LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20131101 PL - England TA - Leuk Lymphoma JT - Leukemia & lymphoma JID - 9007422 RN - 0 (BCL2-like 10 protein) RN - 0 (Proto-Oncogene Proteins c-bcl-2) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Aged, 80 and over MH - Alleles MH - Amino Acid Substitution MH - Bone Marrow/pathology MH - Case-Control Studies MH - DNA Mutational Analysis MH - Female MH - Gene Frequency MH - Genotype MH - Humans MH - Leukemia, Myeloid, Acute/diagnosis/*etiology MH - Male MH - Middle Aged MH - *Mutation MH - Myelodysplastic Syndromes/diagnosis/*etiology MH - Neoplasms, Second Primary/diagnosis/*etiology MH - Odds Ratio MH - Polymorphism, Genetic MH - Proto-Oncogene Proteins c-bcl-2/*genetics MH - Risk MH - Young Adult OTO - NOTNLM OT - BCL2L10 OT - apoptosis OT - myelodysplastic syndrome OT - polymorphisms OT - therapy-related myeloid neoplasms EDAT- 2013/09/21 06:00 MHDA- 2016/03/24 06:00 CRDT- 2013/09/20 06:00 PHST- 2013/11/01 [aheadofprint] AID - 10.3109/10428194.2013.845885 [doi] PST - ppublish SO - Leuk Lymphoma. 2014 Jul;55(7):1538-43. doi: 10.3109/10428194.2013.845885. Epub 2013 Nov 1.