P-GLYCOPROTEIN (PGP) AND LUNG RESISTANCE-RELATED PROTEIN (LRP) EXPRESSION AND FUNCTION IN LEUKEMIC BLAST CELLS

P-glycoprotein (PGP) lung resistance protein (LRP) and multidrug resis tance associated protein (MRP) expressions and function were evaluated by dow cytometry in 65 leukaemic patients (38 acute non-lymphocytic l eukaemias, eight acute lymphocytic leukaemias, 19 Ph-positive chronic myeloid leukaemias in blastic phase). By using the MRK-16, the LRP-56 and the MRPm6 MoAbs, 34% of the cases did not over-express any protein s (-); 24.5% overexpressed (+) only PGP, 11% only LRP, 1.5% only MRP, 24.5% both PGP and LRP, and 4.5% both PGP and MRP. The mean intracellu lar daunorubicin accumulation (IDA) and rhodamine 123 (Rh123) retentio n in the presence or absence of the reversal agent SDZ PSC 833 (PSC) o f the PGP(-)/LRP(-)/MRP(-) cases were comparable to the ones observed in normal leucocytes. With respect to the non-overexpressing cases, th e PGP(-)/LRP(+)/MRP(-) cases showed only an impaired IDA (mean 204+/-2 9; P < 0.001). The PGP(+)/LRP(+)/MRP(-) cases had a defect both in IDA (mean 166+/-47, P < 0.001) and Rh123 retention (mean 0.42+/-0.14; P < 0.001), which were both corrected by PSC. All the PGP(+)/LRP(+)/MRP(- ) cases had a defect in IDA (mean daunorubicin (DNR) accumulation 192/-44; P < 0.001). However, only in 8/16 of them an evident defect in R h123 retention was found. In conclusion, both PGP and LRP over-express ion were common in leukaemia. An impaired IDA was found in all cases o ver-expressing PGP, LRP or both. The study of Rh123 retention could gi ve incorrect information about the blast cells' ability to accumulate cytotoxic drugs in patients over-expressing both PGP and LRP.