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

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

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1
Division Epigenomics and Cancer Risk Factors, German Cancer Research Center, Heidelberg, Germany. rainer.claus@uniklinik-freiburg.de

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.

PMID:
23158571
DOI:
10.1016/j.leukres.2012.10.015
[Indexed for MEDLINE]
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