Differential effects of cladribine and gemcitabine on erythroid and granulocytic progenitors from patients with chronic myeloid leukemia

Chronic myeloid leukemia (CML) is a clonal neoplastic disease that originat es in a pluripotent stem cell. Selection of normal progenitors by graft-pur ging may improve the outcome after autologous transplantation. In our methy lcellulose assays, the nucleoside analogs cladribine (2-CdA) and gemcitabin e (dFdC) shown ed more prominent inhibitory effects on CML than normal bone marrow (BW) progenitors. For dFdC, however, long-term incubations were nec essary to achieve complete inhibition. Deoxycytidine kinase, the key enzyme of both 2-CdA and dFdC metabolisms, was only partially responsible for thi s differential sensitivity. We suggest that 2-CdA and dFdC might be helpful in purging of CML BM cells before autologous BM transplantation. Further s tudies on more primitive cells are warranted. (C) 1999 Elsevier Science Ltd . All rights reserved.