期刊
LEUKEMIA RESEARCH
卷 37, 期 2, 页码 190-196出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.leukres.2012.10.015
关键词
AML; Epigenetics; DNA methylation; Decitabine; DNMT inhibition; Epigenetic therapy
资金
- German Research Council (DFG) [CL 427/2-1]
- DFG [SPP1463, LU 429/7-1, PL 202/3-1, SFB 992-C4]
- German Cancer Aid [108397]
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. (C) 2012 Elsevier Ltd. All rights reserved.
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