Decreased DNA methylation in acute myeloid leukemia patients with DNMT3A mutations and prognostic implications of DNA methylation

Leuk Res. 2012 Sep;36(9):1128-33. doi: 10.1016/j.leukres.2012.05.012. Epub 2012 Jun 28.

Abstract

We examined 79 acute myeloid leukemia (AML) patients for DNA methylation of 12 tumor suppressor genes (TSG) and 24 homeobox domain (Hox) genes, and additionally for mutations in DNMT3A gene. We observed lower levels of DNA methylation (P<0.0001) as well as smaller numbers of concurrently hypermethylated genes (P<0.0001) in patients with DNMT3A mutations. Our study of the impact of DNA methylation on prognosis in intermediate and high risk AML patients revealed a relation between higher DNA methylation and better patients' outcome. Lower DNA methylation was linked with higher relapse rates and an inferior overall survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cohort Studies
  • Cytogenetic Analysis
  • DNA (Cytosine-5-)-Methyltransferases / genetics*
  • DNA Methylation / genetics*
  • DNA Methyltransferase 3A
  • Down-Regulation / genetics
  • Epigenesis, Genetic / physiology
  • Female
  • Gene Expression Regulation, Leukemic / genetics
  • Gene Expression Regulation, Leukemic / physiology
  • Humans
  • Leukemia, Myeloid, Acute / diagnosis*
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / mortality
  • Male
  • Middle Aged
  • Mutation, Missense* / physiology
  • Prognosis
  • Survival Analysis
  • Young Adult

Substances

  • DNMT3A protein, human
  • DNA (Cytosine-5-)-Methyltransferases
  • DNA Methyltransferase 3A