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

被引：22

作者：

Claus, Rainer ^{[1
,2
]}

Pfeifer, Dietmar ^{[2
]}

Almstedt, Maika ^{[2
]}

Zucknick, Manuela ^{[3
]}

Hackanson, Bjoern ^{[2
]}

Plass, Christoph ^{[1
]}

Luebbert, Michael ^{[2
]}

机构：

[1] German Canc Res Ctr, Div Epigen & Canc Risk Factors, Heidelberg, Germany

[2] Univ Freiburg, Dept Hematol Oncol, Med Ctr, D-79106 Freiburg, Germany

[3] German Canc Res Ctr, Div Biostat, Heidelberg, Germany

来源：

LEUKEMIA RESEARCH | 2013年 / 37卷 / 02期

关键词：

AML; Epigenetics; DNA methylation; Decitabine; DNMT inhibition; Epigenetic therapy; MYELODYSPLASTIC SYNDROME MDS; CONVENTIONAL CARE REGIMENS; ELDERLY-PATIENTS; OLDER PATIENTS; PHASE-III; 1ST-LINE TREATMENT; GENE-EXPRESSION; SUPPORTIVE CARE; OPEN-LABEL; AZACITIDINE;

D O I：

10.1016/j.leukres.2012.10.015

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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.

引用

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页码：190 / 196

页数：7

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