ANTHRACYCLINE DRUGS AND MDR EXPRESSION IN HUMAN LEUKEMIA

We investigated the expression of P-glycoprotein (P-gp) in 50 adults w ith de novo acute myeloid leukemia (AML) at the initial diagnosis in o rder to further define the relationship between the presence of P-gp o n leukemic cells and the efficacy of two different anthracycline drugs , Daunorubicin (DNR) and Idarubicin (IRR), in terms of remission, indu ction and survival. We found that 30 (60%) of the 50 patients were neg ative for P-gp expression (group 1) and 20 patients (40%) were positiv e (group 2) for P-gp expression by MRK16 MoAb using a cut of 10% posit ive cells. Among the 50 patients, 35 (70%) obtained complete remission (CR); depending on P-gp expression the CR rate was 80% for group 1 an d 45% for group 2 (p < 0.005). The median duration of overall survival (OS) was 20 months for patients in group 1, compared to 10 months for patients in group 2 (p < 0.005). Regarding the anthracycline used, no difference in CR has been observed in patients of group 1 (75% CTR wi th DNR versus 90% CR with IDR); on the contrary in group 2 we observed 40% CR with DNR versus 70% CR with IDR (p < 0.005). No significant di fference has been achieved in group 1 terms of median duration of over all survival between DNR and IDR regimen; on the contrary the median d uration of OS in patients of group 2 treated with IDR regimen was sign ificantly longer than DNR regimen (p < 0.005). These results confirm t he prognostic value of P-gp expression in AML at diagnosis and we sugg est that Idarubicin could he a valid anthracycline drug for reversing multidrug resistance.