Expression of the multidrug transporter, P-glycoprotein, in chronic myelogenous leukaemia cells in blast crisis.

The overexpression of a cell-surface glycoprotein termed P-glycoprotein (P-gp) is frequently associated with multidrug resistance (MDR) in cell lines in vitro. To evaluate the implications of P-gp expression in clinical drug-resistance, we examined the expression of P-gp in fresh leukaemia cells from chronic myelogenous leukaemia (CML) patients in blast crisis. By using immunoblotting with a monoclonal antibody against P-gp, C219, we showed that leukaemia cells from three CML patients in blast crisis were P-gp negative at the stage when these patients were in complete remission, and that the cells showed high levels of P-gp expression at times when the same patients had relapsed and had not responded to chemotherapy. Six out of 11 patients (nine in the refractory state) were P-gp positive and they rarely responded to chemotherapy. These data suggest that the expression of P-gp is closely associated with drug-resistance in CML.