Expression of the multidrug transporter, P-glycoprotein, in acute leukemia cells and correlation to clinical drug resistance.
The overexpression of a cell-surface glycoprotein termed P-glycoprotein (P-gp) is frequently associated with multi-drug resistance (MDR) in cell lines in vitro. To evaluate the implications of P-gp expression in clinical drug resistance, the authors examined the expression of P-gp in leukemia cells from patients with acute myelogenous leukemia (AML) and those with acute lymphoblastic leukemia (ALL) at initial presentation and relapse, using immunoblotting with a monoclonal antibody against P-gp, C219. Nine of 17 patients with AML and four of 11 patients with ALL had P-gp-positive results at the initial presentation, and most P-gp-positive patients did not respond to chemotherapy. Four of seven patients at the relapsed stage and all three patients with preceding myelodysplastic syndrome had P-gp-positive results. The expression of P-gp and clinical refractoriness to chemotherapy were highly correlated. These data indicate that the expression of P-gp is closely related to clinical drug resistance in acute leukemia.
Kuwazuru
Y
Y
Cancer Research Institute, Faculty of Medicine, Kagoshima University, Japan.
Yoshimura
A
A
Hanada
S
S
Utsunomiya
A
A
Makino
T
T
Ishibashi
K
K
Kodama
M
M
Iwahashi
M
M
Arima
T
T
Akiyama
S
S
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000378:metabolism / Q000627:therapeutic use; D004351:Drug Resistance; D005260:Female; D006801:Humans; D015151:Immunoblotting; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000378:metabolism*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins