The effect of 5-azacytidine and its analogues on blast cell renewal in acute myeloblastic leukemia

Blast cells from patients with acute myeloblastic leukemia were exposed to 5-azacytidine (5-aza) and its analogues 5-aza 2′-deoxycytidine (5- aza-dr) and 6-azacytidine (6-aza). Simple negative exponential survival curves were obtained for the three drugs, but the sensitivity varied; 5- aza-dr was most toxic, 6-aza was least toxic, and 5-aza was intermediate. Colonies surviving drug exposure were replated; 5-aza and 5-aza-dr were found to increase secondary plating efficiency, whereas 6- aza was inactive. The findings provide indirect evidence for a role for DNA methylation in the regulation of blast cell self-renewal.