Prolonged administration of methyl transferase inhibitors may increase response rates in myelodysplastic syndromes (MDS). Fourteen MDS patients with anemia and less than 10% marrow blasts received azacitidine 50 mg/m(2) thrice weekly for 2 weeks every 4 weeks; 7 also received weekly erythropoietin. The response rate of 43% did not improve the rates reported with other azacitidine administration schedules, so the study was closed. A decreased apoptosis of primitive erythroid progenitors and increased expression of BclX(L) was observed with treatment in responding patients compared to non-responders. Azacitidine may modulate BclX(L) and improve erythropoiesis through reduction of apoptosis in primitive erythroid progenitor population in MDS.
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