EFFECT OF VERAPAMIL ON DAUNORUBICIN ACCUMULATION IN HUMAN LEUKEMIC-CELLS WITH DIFFERENT LEVELS OF MDR1 GENE-EXPRESSION

The purpose of the present study was to evaluate the distribution of t he multiple drug resistance phenotype in leukemic cells with different levels of mdr1 gene expression. Peripheral leukemic cells from 8 pati ents (5 with detectable and 3 with undetectable mdr1 RNA levels) were incubated with daunorubicin (1 muM) in the absence and presence of ver apamil (6.6 muM). Daunorubicin accumulation in individual cells was an alysed by flow cytometry. Verapamil increased (16-45%) the mean daunor ubicin accumulation in 7 of the 8 cell samples. In cells from 4 of the se 7 patients, the fluorescence histograms showed a general increase o f daunorubicin accumulation. The increase was limited to a small subpo pulation of cells in one patient. In the remaining two patients an inc rease of daunorubicin accumulation was seen in the majority of cells, while cells with the highest accumulation were unaffected. In conclusi on, verapamil can increase daunorubicin accumulation in leukemic cells with and without detectable mdr1 gene expression and the increase see ms to affect the majority of the cell population.