Hemin Enhances the Sensitivity of Erythroleukemia Cells to 1-β-d-Arabinofuranosylcytosine by Both Activation of Deoxycytidine Kinase and Reduction of Cytidine Deaminase Activity¹

The sensitivity of human myelogenous leukemia cells to 1-β-d-arabinofuranosylcytosine (ara-C) during induction of differentiation was examined. Treatment with hemin greatly increased the sensitivity of erythroid leukemia cells to ara-C. The enhancement of ara-C sensitivity by hemin was not as remarkable in nonerythroid leukemia cells. Hemin altered the metabolism of ara-C in human erythroleukemia K562 cells by reducing ara-C deaminase activity, increasing intracellular accumulation of ara-C, and activating the nucleoside kinases. These alterations may be involved in the enhancing effect of hemin on sensitivity of ara-C. These results suggest that some inducers of differentiation potentiate the antileukemic effect of ara-C on human erythroleukemia cells.