Decitabine induces very early in vivo DNA methylation changes in blasts from patients with acute myeloid leukemia

Leuk Res. 2013 Feb;37(2):190-6. doi: 10.1016/j.leukres.2012.10.015. Epub 2012 Nov 15.

Abstract

In vivo effects of the DNA hypomethylating agent 5-aza-2'-deoxycytidine (DAC) upon the epigenome of acute myeloid leukemia (AML) patients are scarcely studied in primary blasts. Here, we sequentially assessed DNA methylation and transcriptome changes in myeloblasts of DAC-treated AML patients. DNA methylation changes were detected in all patients already after the first series of infusion (median: 6 days). LINE1 analysis indicated global DNA methylation decrease in 7/8 patients. Gene-specific hypomethylating effects were not directly linked to mRNA expression changes. In conclusion, complex DAC-induced DNA methylation changes occur very early and imply mechanisms distinct from non-hypomethylating cytosine analogs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antimetabolites, Antineoplastic / pharmacology*
  • Antimetabolites, Antineoplastic / therapeutic use
  • Azacitidine / analogs & derivatives*
  • Azacitidine / pharmacology
  • Azacitidine / therapeutic use
  • Cluster Analysis
  • CpG Islands
  • DNA Methylation / drug effects*
  • Decitabine
  • Epigenesis, Genetic
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Leukemic / drug effects
  • Hematopoietic Stem Cells / metabolism
  • Hematopoietic Stem Cells / pathology
  • Humans
  • Leukemia, Myeloid, Acute / drug therapy
  • Leukemia, Myeloid, Acute / genetics*
  • Male

Substances

  • Antimetabolites, Antineoplastic
  • Decitabine
  • Azacitidine