Comparison between Anthracyclines and Rhodamine-123 Accumulation in Chronic Lymphoid Leukemia: Effect of Cyclosporin A and Verapamil

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Abstract
Multidrug resistance in leukemic cells is associated with decreased drug accumulation. A resistant cell line and cells from 11 patients with chronic lymphoid leukemia B were used for the evaluation of intracellular accumulation of daunorubicin (DNR), idarubicin (IDA), epirubicin (EPI) and rhodamine-123 (Rh-123). Cyclosporin A (CSA) and verapamil were used to test their modulatory effects on anthracyclines and the fluorescent dye. In leukemic samples there was a tendency for a lower accumulation index in samples tested with Rh-123 as compared to anthracyclines. IDA was a poorer substrate to P-glycoprotein (Pgp) than two of its analogues, e.g. DNR and EPI. A good correlation (80%) was found between Rh-123 accumulation and Pgp expression by phosphatase-anti-alkaline phosphatase. A strict correlation (100%) was found between modulation by CSA of Rh-123 accumulation and immunoreactivity to Pgp. Two discordant results were seen suggesting that other mechanisms of resistance could be present. The Rh-123 accumulation test seems to give a better indication than anthracyclines, however, it is not selective and may allow the detection of other drug-transport pumps.

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