DISCORDANT P-GLYCOPROTEIN ANTIGEN EXPRESSION AND TRANSPORT FUNCTION IN ACUTE MYELOID-LEUKEMIA

Expression of the multidrug resistance efflux pump P-glycoprotein (Pgp ) was measured in a series of AML patients using two flow cytometry me thods. Transport function was assessed by measuring the modulating eff ect of the Pgp inhibitor cyclo-sporin A (CsA) on the cellular accumula tion of daunorubicin, and Pgp antigen expression by surface immunofluo rescence using the MRK-16 antibody. Both methods showed a wide range o f values for Pgp expression between individual patients, but in contra st to a series of cell lines expressing Pgp there was no correlation b etween antigen expression and transport function in the clinical sampl es. As previously reported for chronic lymphocytic leukemia (CLL), pre treatment with neuraminidase markedly improved MRK-16 staining in some cases, indicating that abnormal glycosylation can cause epitope maski ng in AML blasts, Because experience with cell lines shows that Pgp ex pression is a continuous variable which correlates with the level of d rug resistance, rather than the 'positive' or 'negative' which are fre quently reported by clinical flow cytometry laboratories, we used a ca libration procedure to estimate the actual number of Pgp molecules exp ressed in the AML samples. Despite the additional refinements of neura minidase treatment and antigen quantification, the correlation between Pgp antigen expression and daunorubicin accumulation remained extreme ly weak (r = 0.11; P = 0.63). It is suggested that the assay for trans port function can detect molecules that affect daunorubicin accumulati on but are antigenically distinct from classical P-glycoprotein. Heter ogeneity of multidrug resistance efflux pumps might in part explain th e relatively weak prognostic significance of immunofluorescence detect ion of Pgp in AML patients.