FLOW CYTOMETRIC STUDY OF IDARUBICIN AND DAUNORUBICIN ACCUMULATION AND THE 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 idarubicin (IDA) and daunorubicin (DNR) and the effect of verapamil (VRP) on 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 results were observed in fresh leukemic blasts from 25 patients with ANLL (IDA Ace superior to DNR Ace: p < 0.0001; higher VRP index for DNR than for IDA: p < 0.01). The higher Ace of IDA than DNR seen in fresh leukemic cells could explain the better clinical efficacy of IDA reported in patients with ANLL.