Prognostic and biologic significance of DNMT3B expression in older patients with cytogenetically normal primary acute myeloid leukemia

DNMT3B encodes a DNA methyltransferase implicated in aberrant epigenetic changes contributing to leukemogenesis. We tested whether DNMT3B expression, measured by NanoString nCounter assay, associates with outcome, gene and microRNA expression and DNA methylation profiles in 210 older (⩾60 years) adu...

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Bibliographic Details
Published in:Leukemia 2015-03, Vol.29 (3), p.567-575
Main Authors: Niederwieser, C, Kohlschmidt, J, Volinia, S, Whitman, S P, Metzeler, K H, Eisfeld, A-K, Maharry, K, Yan, P, Frankhouser, D, Becker, H, Schwind, S, Carroll, A J, Nicolet, D, Mendler, J H, Curfman, J P, Wu, Y-Z, Baer, M R, Powell, B L, Kolitz, J E, Moore, J O, Carter, T H, Bundschuh, R, Larson, R A, Stone, R M, Mrózek, K, Marcucci, G, Bloomfield, C D
Format: Article
Language:English
Subjects:
Acute myeloid leukemia
Age Factors
Aged
Aged, 80 and over
Cancer
Cytarabine - therapeutic use
Daunorubicin - therapeutic use
Deoxyribonucleic acid
DNA
DNA (Cytosine-5-)-Methyltransferases - genetics
DNA Methylation
DNA methyltransferase
DNA Methyltransferase 3B
DNA microarrays
DNA sequencing
Female
Gene expression
Gene Expression Profiling
Gene Expression Regulation, Leukemic
Genes
Genetic research
Health aspects
Humans
Induction Chemotherapy
Karyotyping
Leukemia
Leukemia, Myeloid, Acute - diagnosis
Leukemia, Myeloid, Acute - drug therapy
Leukemia, Myeloid, Acute - genetics
Leukemia, Myeloid, Acute - mortality
Leukemogenesis
Male
Microarray Analysis
MicroRNA
MicroRNAs
MicroRNAs - genetics
Middle Aged
miRNA
Myeloid leukemia
Oncology, Experimental
Prognosis
Regulatory mechanisms (biology)
Ribonucleic acid
RNA
Survival
Survival Analysis
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Summary:DNMT3B encodes a DNA methyltransferase implicated in aberrant epigenetic changes contributing to leukemogenesis. We tested whether DNMT3B expression, measured by NanoString nCounter assay, associates with outcome, gene and microRNA expression and DNA methylation profiles in 210 older (⩾60 years) adults with primary, cytogenetically normal acute myeloid leukemia (CN-AML). Patients were dichotomized into high versus low expressers using median cut. Outcomes were assessed in the context of known CN-AML prognosticators. Gene and microRNA expression, and DNA methylation profiles were analyzed using microarrays and MethylCap-sequencing, respectively. High DNMT3B expressers had fewer complete remissions (CR; P=0.002) and shorter disease-free (DFS; P=0.02) and overall (OS; P
ISSN:0887-6924
1476-5551
DOI:10.1038/leu.2014.267