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Decitabine in myelodysplastic syndromes

Elias Jabbour, Hagop M Kantarjian, Guillermo Garcia-Manero and Jean-Pierre J Issa

Decitabine (5-aza-2’-deoxycytidine), a cytosine analog, inhibits DNA methylation and has dual effects on neoplastic cells, including the reactivation of silenced genes and differentiation at low doses, and cytotoxicity at high doses. Decitabine has promising clinical efficacy in the treatment of myelodysplastic syndromes (a heterogeneous group of bone marrow malignancies), with evidence of target modulation (hypomethylation) and a favorable toxicity profile. Optimal dosing schedules of decitabine in myelodysplastic syndrome are those that maximize hypomethylation (low dose, high dose intensity, multiple cycles). However, the molecular mechanisms of in vivo response to decitabine are still unclear. Combination therapies that augment decitabine’s epigenetic effect, or take advantage of gene activation, will likely improve clinical responses and may extend its use to the treatment of other malignancies.