Decitabine in Chronic Leukemias

5-Aza-2′-deoxycitidine (decitabine, Dacogen™, Bloomington, MN) is a cytosine analogue that promotes hypomethylation of DNA and has documented efficacy in myeloid malignancies. Indeed, promising clinical results have been observed in acute myeloid leukemia (AML) and the myelodysplastic syndromes (MDS). Aberrant methylation has also been found in chronic leukemias, providing a rationale for investigating the use of decitabine in these diseases. There is clear evidence of molecular (hypomethylation) as well as hematologic and cytogenetic responses to decitabine in chronic myelogenous leukemia of all phases, including in patients resistant to imatinib mesylate. Clinical trials of decitabine in chronic lymphocytic leukemia are ongoing. There are many unanswered questions regarding optimizing this treatment for chronic leukemias, but successful proof-of-concept studies for hypomethylating agents move us closer to approaches that may have a significant impact on patient outcomes.