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.
Kuwazuru
Y
Y
Cancer Research Institute, Faculty of Medicine, Kagoshima University, Japan.
Yoshimura
A
A
Hanada
S
S
Ichikawa
M
M
Saito
T
T
Uozumi
K
K
Utsunomiya
A
A
Arima
T
T
Akiyama
S
S
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001752:Blast Crisis / Q000188:drug therapy / Q000378:metabolism*; D004351:Drug Resistance / Q000502:physiology*; D005260:Female; D006801:Humans; D015151:Immunoblotting; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D014407:Tumor Cells, Cultured / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins