Common expression of the multidrug resistance marker P-glycoprotein in B-cell chronic lymphocytic leukaemia and correlation with in vitro drug resistance.
The expression of P-glycoprotein (Pgp), which is associated with multidrug resistance (MDR), was investigated in 20 B-cell chronic lymphocytic leukaemia (B-CLL) patients by flow cytometry using two Pgp-specific monoclonal antibodies (mAb), MRK-16 which recognizes an extracellular epitope, and JSB-1 which recognizes an intracellular epitope. Sixteen (80%) patients were positive with MRK-16 whereas all patients were positive with JSB-1. The proportion of Pgp-positive lymphocytes from each patient sample varied from 2-94% for MRK-16 and 20-93% for JSB-1. There was no correlation between the level of positivity and disease stage or treatment history. In vitro drug resistance to vincristine (VCR) and doxorubicin (DOX) was determined by the colorimetric MTT assay. All patients were resistant to one or both drugs being consistent with the expression of Pgp. There was no correlation between the level of resistance and disease stage or drug treatment. We investigated the expression of Pgp in the normal counterpart of the B-CLL cells, CD5+CD19+ B-lymphocytes. A minor subpopulation (3%) of CD5+CD19+ lymphocytes isolated from normal controls expressed Pgp suggesting that these cells may be the potential precursors to the B-CLL cell. We conclude that Pgp expression and drug resistance are inherent characteristics of the B-CLL lymphocyte.
Sparrow
R L
RL
Pathology Service, Alfred Hospital, Prahran, Victoria, Australia.
Hall
F J
FJ
Siregar
H
H
Van der Weyden
M B
MB
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal / Q000276:immunology; D002352:Carrier Proteins / Q000378:metabolism*; D002470:Cell Survival; D004317:Doxorubicin / Q000494:pharmacology; D004351:Drug Resistance; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D014750:Vincristine / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D014750:Vincristine; D004317:Doxorubicin