MDR1 GENE-EXPRESSION AND DRUG-RESISTANCE OF AML CELLS

We investigated the cellular drug resistance to aclarubicin (Acla), cy tosine arabinoside (Ara-C), daunorubicin (Dau), doxorubicin (Dox), eto poside (Etop) and mitoxantrone (Miter) using the MTT assay at time of disease presentation in 93 cases of acute myeloid leukaemia (AML). In 31 cases we concomitantly investigated MDR1 (multiple drug resistance 1 gene) expression (semi-quantitative competitive RT-PCR) of the leuka emic cells. Drug resistance towards Dau, Dox and Etop was correlated t o the MDR1 expression of the AML cells (P<0.05) with high MDR1 express ion being associated with high drug resistance towards these drugs. Al though the data did not allow firm conclusions to be drawn on the corr elation between MDR1 expression and drug resistance towards Ara-C and Mitox, the drug resistance towards Acla clearly was not correlated to, or dependent on, the MDR1 expression level of the AML blast cells. In addition, when examining the cross-activities among the six drugs dis tinct patterns emerged. Thus, high to very high degrees of cross-activ ity were found to exist between Dau, Dox, Etop and Mitox, whereas Ara- C had moderate cross-activity with the other drugs except Acla, which showed absent to moderate cross-activity with the other drugs, We conc lude that: MDR1 gene expression is of significance for cellular drug r esistance towards specific (MDR1-related) drugs in AML, whereas it is not of significance regarding drug resistance towards other drugs, whi ch is the case with the anthracycline Acla. We suggest that in the pla ce of other more or less complicated ways to circumvent MDR1-mediated drug resistance, Acla may be used to replace Dau, Dox and other MDR1-r elated drugs if proven as potent as the drug it is to substitute.