DIPYRIDAMOLE ENHANCEMENT OF DRUG-SENSITIVITY IN ACUTE LYMPHOBLASTIC-LEUKEMIA CELLS

The effect of dipyridamole (DPM) on cell sensitivity to anticancer dru gs was examined in acute lymphoblastic leukemia (ALL) cell lines. We e stablished two ALL cell lines (KMO-90 and KMO-R) from bone marrow samp les of a 12-year-old girl with ALL. The drug concentrations needed to reduce optical density to 50% of that of control cells (IC50) showed t hat KMO-R was about twofold more resistant to doxorubicin (DOX), mitxa ntrone (MIT), vincristine (VCR), and etoposide (VP-16) than was KMO-90 . Considering that both KMO-90 and KMO-R were established from a patie nt with ALL at the time of presentation and relapse, respectively, the se two cell lines might be novel and useful models for research into t he acquisition of drug resistance in ALL cells. Although cytotoxicity of DPM in KMO-90 was about 6% at 1 mug/ml, DPM enhanced cell sensitivi ty to DOX, MIT, VCR, and VP-16 at this concentration. Cytotoxicity of DPM in KMO-R was less than 5% at 1, 5, and 10 mug/ml. In KMO-R, DPM en hanced cell sensitivity to these four drugs in a dose-dependent manner . The plasma concentrations achieved by oral administration of DPM is about 1 mu/ml. At clinically achievable concentrations, DPM enhanced c ell sensitivity to DOX, MIT, VCR, and VP-16 in both KMO-90 and KMO-R, thus showing DPM to be a useful agent for potentiating anticancer chem otherapy of hematopoietic malignancy. (C) 1993 Wiley-Liss, Inc.