title: Decitabine induces very early in vivo DNA methylation changes in blasts from patients with acute myeloid leukemia.
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.
authors.affiliation: Division Epigenomics and Cancer Risk Factors, German Cancer Research Center, Heidelberg, Germany. rainer.claus@uniklinik-freiburg.de
authors.forename: Rainer
authors.initials: R
authors.lastname: Claus
authors.forename: Dietmar
authors.initials: D
authors.lastname: Pfeifer
authors.forename: Maika
authors.initials: M
authors.lastname: Almstedt
authors.forename: Manuela
authors.initials: M
authors.lastname: Zucknick
authors.forename: Björn
authors.initials: B
authors.lastname: Hackanson
authors.forename: Christoph
authors.initials: C
authors.lastname: Plass
authors.forename: Michael
authors.initials: M
authors.lastname: Lübbert
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology* / Q000627:therapeutic use; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D016000:Cluster Analysis; D018899:CpG Islands; D019175:DNA Methylation / Q000187:drug effects*; D000077209:Decitabine; D044127:Epigenesis, Genetic; D005260:Female; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000235:genetics*; D008297:Male
chemical_list: D000964:Antimetabolites, Antineoplastic; D000077209:Decitabine; D001374:Azacitidine