FLOW CYTOMETRIC STUDY OF IDARUBICIN AND DAUNORUBICIN ACCUMULATION ANDTHE EFFECT OF VERAPAMIL IN LEUKEMIC-CELL LINES AND FRESH CELLS FROM PATIENTS WITH ACUTE NONLYMPHOBLASTIC LEUKEMIA

By using flow cytometry, the intracellular accumulation (Ace) of idaru bicin (IDA) and daunorubicin (DNR) and the effect of verapamil (VRP) o n both anthracycline accumulation (VRP index) were studied in leukemic cell lines (K562 and HL60 and their two DNR-resistant subclones) and fresh leukemic cells. IDA accumulated more than DNR in both parental ( K562: p < 0.03 and HL60: 0.09) and resistant cell lines (p < 0.01 for both cell lines) irrespective of whether or not they were treated with VRP. VRP index was higher for DNR than for IDA (p < 0.05). Similar re sults were observed in fresh leukemic blasts from 25 patients with ANL L (IDA Ace superior to DNR Ace: p < 0.0001; higher VRP index for DNR t han for IDA: p < 0.01). The higher Ace of IDA than DNR seen in fresh l eukemic cells could explain the better clinical efficacy of IDA report ed in patients with ANLL.