EFFECT OF DIFFERENTIATING AGENTS ON MODULATION OF MDR1 GENE-EXPRESSION IN MULTIDRUG-RESISTANT HEMATOPOIETIC HL60 DNR CELL-LINE/

The phenomenon of multidrug resistance (MDR) is frequently encountered in clinical situations, and could contribute to the failure of chemot herapy in acute leukemia. Preliminary studies have suggested that MDR1 gene expression in normal hematopoietic stem cells might be downregul ated during differentiation. In the present study, we induced a multid rug-resistant promyelocytic leukemia cell line, HL60/DNR, to myeloid d ifferentiation by exposure to all-trans retinoid acid and dimethyl sul foxide (DMSO). We found that HL60/DNR cells retained the ability to re spond to the differentiation stimulus. However, although MTT assays re vealed a slight decrease of IC50 in differentiated cells, neither effl ux of daunorubicin (DNR), nor expression of P-glycoprotein (P-gp), nor quantity of MDR1 mRNA has been downregulated in differentiated cells. We can conclude, therefore, that MDR1 gene expression in this multidr ug-resistant myeloid cell line is not modified by induction of its dif ferentiation.