P-glycoprotein (PGP), lung resistance-related protein (LRP) and multidrug resistance-associated protein (MRP) expression in acute promyelocytic leukaemia

We analysed the expression of three drug transporter proteins [p-glycoprote in (PGP), lung resistance-related protein (LRP) and multidrug resistance-as sociated protein (MRP1)] involved in anthracycline resistance that are freq uently overexpressed in poor-risk adult acute non-lymphocytic leukaemia (AN LL), in 23 acute promyelocytic leukaemia (APL) patients at onset managed at a single institution, Cellular daunorubicin accumulation was also evaluate d. At onset, no case had PGP or MRP1 expression that exceeded that of non-m ultidrug-resistant (MDR) cell lines. Only one case showed LRP overexpressio n, No peculiar MDR features distinguished the seven patients who relapsed f rom those who maintained complete remission, In the onset vs. first relapse , only one patient showed an increased (threefold) PGP expression at relaps e. At second relapse, three out of four patients showed a PGP expression tw o- to threefold higher than baseline values, These results are consistent w ith the view that low PGP, LRP and MRP1 expression and the absence of defec ts in intracellular drug accumulation may account for the peculiarly high s ensitivity of APLs to anthracycline. It does not support: the screening of MDR markers in APL patients at onset as predicting factors of early relapse . The results suggest that no significant changes in PGP, LRP or MRP1 expre ssion are likely to occur at first relapse, In contrast, PGP expression is likely to increase later in the patient history as a result of additional c hemotherapy courses.