CpG methylation patterns and decitabine treatment response in acute myeloid leukemia cells and normal hematopoietic precursors.

ABSTRACT: The DNA hypomethylating drug decitabine maintains normal hematopoietic stem cell (HSC) self-renewal but induces terminal differentiation in acute myeloid leukemia (AML) cells. The basis for these contrasting cell fates, and for selective CpG hypomethylation by decitabine, is poorly understood. Promoter CpGs, with methylation measured by microarray, were classified by the direction of methylation change with normal myeloid maturation. In AML cells, the methylation pattern at maturation-responsive CpGs suggested at least partial maturation. Consistent with partial maturation, in gene expression analyses, AML cells expressed high levels of the key lineage-specifying factor CEBPA, but relatively low levels of the key late-differentiation driver CEBPE. In methylation analysis by mass spectromet

SUBMITTER: Negrotto S 

PROVIDER: S-EPMC3217177 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature