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

Publication ,  Journal Article
Niederwieser, C; Kohlschmidt, J; Volinia, S; Whitman, SP; Metzeler, KH; Eisfeld, A-K; Maharry, K; Yan, P; Frankhouser, D; Becker, H; Schwind, S ...
Published in: Leukemia
March 2015

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<0.001) survival. In multivariable analyses, high DNMT3B expression remained an independent predictor of lower CR rates (P=0.04) and shorter DFS (P=0.04) and OS (P=0.001). High DNMT3B expression associated with a gene expression profile comprising 363 genes involved in differentiation, proliferation and survival pathways, but with only four differentially expressed microRNAs (miR-133b, miR-148a, miR-122, miR-409-3p) and no differential DNA methylation regions. We conclude that high DNMT3B expression independently associates with adverse outcome in older CN-AML patients. Gene expression analyses suggest that DNMT3B is involved in the modulation of several genes, although the regulatory mechanisms remain to be investigated to devise therapeutic approaches specific for these patients.

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Published In

Leukemia

DOI

EISSN

1476-5551

Publication Date

March 2015

Volume

29

Issue

3

Start / End Page

567 / 575

Location

England

Related Subject Headings

  • Survival Analysis
  • Prognosis
  • Middle Aged
  • Microarray Analysis
  • MicroRNAs
  • Male
  • Leukemia, Myeloid, Acute
  • Karyotyping
  • Induction Chemotherapy
  • Immunology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Niederwieser, C., Kohlschmidt, J., Volinia, S., Whitman, S. P., Metzeler, K. H., Eisfeld, A.-K., … Bloomfield, C. D. (2015). Prognostic and biologic significance of DNMT3B expression in older patients with cytogenetically normal primary acute myeloid leukemia. Leukemia, 29(3), 567–575. https://doi.org/10.1038/leu.2014.267
Niederwieser, C., J. Kohlschmidt, S. Volinia, S. P. Whitman, K. H. Metzeler, A. -. K. Eisfeld, K. Maharry, et al. “Prognostic and biologic significance of DNMT3B expression in older patients with cytogenetically normal primary acute myeloid leukemia.Leukemia 29, no. 3 (March 2015): 567–75. https://doi.org/10.1038/leu.2014.267.
Niederwieser C, Kohlschmidt J, Volinia S, Whitman SP, Metzeler KH, Eisfeld A-K, et al. Prognostic and biologic significance of DNMT3B expression in older patients with cytogenetically normal primary acute myeloid leukemia. Leukemia. 2015 Mar;29(3):567–75.
Niederwieser, C., et al. “Prognostic and biologic significance of DNMT3B expression in older patients with cytogenetically normal primary acute myeloid leukemia.Leukemia, vol. 29, no. 3, Mar. 2015, pp. 567–75. Pubmed, doi:10.1038/leu.2014.267.
Niederwieser C, Kohlschmidt J, Volinia S, Whitman SP, Metzeler KH, Eisfeld A-K, Maharry K, Yan P, Frankhouser D, Becker H, Schwind S, Carroll AJ, Nicolet D, Mendler JH, Curfman JP, Wu Y-Z, Baer MR, Powell BL, Kolitz JE, Moore JO, Carter TH, Bundschuh R, Larson RA, Stone RM, Mrózek K, Marcucci G, Bloomfield CD. Prognostic and biologic significance of DNMT3B expression in older patients with cytogenetically normal primary acute myeloid leukemia. Leukemia. 2015 Mar;29(3):567–575.

Published In

Leukemia

DOI

EISSN

1476-5551

Publication Date

March 2015

Volume

29

Issue

3

Start / End Page

567 / 575

Location

England

Related Subject Headings

  • Survival Analysis
  • Prognosis
  • Middle Aged
  • Microarray Analysis
  • MicroRNAs
  • Male
  • Leukemia, Myeloid, Acute
  • Karyotyping
  • Induction Chemotherapy
  • Immunology