Therapeutics and DNA Methylation Inhibitors

Dysregulation of cellular epigenetic machinery is linked to the pathogenesis of a number of malignancies and has been studied extensively in the myelodysplastic syndromes and acute myeloid leukemia. Alteration of DNA methylation in cancer cells results in transcriptional silencing of tumor suppressor genes. DNA methyltransferase inhibitors, such as azacitidine and decitabine, have been used to reexpress these genes and have demonstrated therapeutic benefit in both benign and malignant diseases. In this chapter, we discuss the clinical application of demethylating agents, the data that has led to their approval in hematologic diseases, and future potential uses of these agents both alone and in combination.