Clinical development of demethylating agents inhematology

摘要

The term epigenetics refers to the heritable changes in gene expression that are notassociated with a change in the actual DNA sequence. Epigenetic dysregulation islinked to the pathogenesis of a number of malignancies and has been studiedextensively in myelodysplastic syndromes and acute myeloid leukemia. DNA methylationis frequently altered in cancerous cells and likely results in transcriptionalsilencing of tumor suppressor genes. Re-expression of these genes by inhibition ofthe DNA methyltransferases has been successful in the treatment of benign andmalignant disease. In this Review, we discuss the clinical development ofdemethylating agents in hematology, with a focus on azacitidine and decitabine.