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

作者：Claus Rainer^*; Pfeifer Dietmar; Almstedt Maika; Zucknick Manuela; Hackanson Bjoern; Plass Christoph; Luebbert Michael

来源：Leukemia Research, 2013, 37(2): 190-196.

DOI：10.1016/j.leukres.2012.10.015

• AML
• Epigenetics
• DNA methylation
• Decitabine
• DNMT inhibition
• Epigenetic therapy

In vivo effects of the DNA hypomethylating agent 5-aza-2%26apos;-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.

• 出版日期2013-2