DEVELOPMENT OF DRUG-RESISTANCE IS REDUCED WITH IDARUBICIN RELATIVE TOOTHER ANTHRACYCLINES

Multidrug resistance (MDR) is associated with poor prognosis in leukem ia, and anthracyclines, which are used in the treatment of leukemia, a re associated with the expression of P-glycoprotein and the developmen t of MDR. We report here that idarubicin, a new anthracycline approved for use in the treatment of acute myelogenous leukemia (AML), did not induce P-glycoprotein expression in the K562 human leukemia cell line under conditions where daunorubicin, doxorubicin and epirubicin did i nduce expression of P-glycoprotein. The P-glycoprotein expressing, mul tidrug resistant sublines developed to daunorubicin (K/DNR), doxorubic in (K/DOX) and epirubicin (K/EPR) were cross-resistant to the other an thracyclines and to vinblastine, taxol, colchicine and actinomycin D, but were not resistant to Idarubicin or etoposide. The idarubicin trea ted subline, K/IDA, was only resistant to taxol but was 12-fold sensit ized to etoposide, suggesting that Idarubicin had affected topoisomera se II in this subline.