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J Clin Invest. 2014 Jan;124(1):40-6. doi: 10.1172/JCI69739. Epub 2014 Jan 2.

Clinical development of demethylating agents in hematology.

Abstract

The term epigenetics refers to the heritable changes in gene expression that are not associated with a change in the actual DNA sequence. Epigenetic dysregulation is linked to the pathogenesis of a number of malignancies and has been studied extensively in myelodysplastic syndromes and acute myeloid leukemia. DNA methylation is frequently altered in cancerous cells and likely results in transcriptional silencing of tumor suppressor genes. Re-expression of these genes by inhibition of the DNA methyltransferases has been successful in the treatment of benign and malignant disease. In this Review, we discuss the clinical development of demethylating agents in hematology, with a focus on azacitidine and decitabine.

PMID:
24382388
PMCID:
PMC3871232
DOI:
10.1172/JCI69739
[Indexed for MEDLINE]
Free PMC Article

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