Quantification of P-glycoprotein in chronic lymphocytic leukemia by flow cytometry.
The P-glycoprotein (P-gp) was investigated in 40 patients with chronic lymphocytic leukemia by immunological, functional and quantitative assays. The proportion of positive cases with the anti-Pgp McAb UIC2 was 30% and increased to 64% after neuraminidase treatment (p = 0.002). Fifty-six per cent of cases were positive with the functional test with rhodamine 123 and verapamil. A negative correlation was found between the number of cells stained with the McAb and the functional test (p = 0.006). The mean of P-gp molecules was 2509 +/- 2805 molecules per cell; these values were higher than in the control K562 cell line in the majority of cases. The number of positive cases and P-gp molecules were higher in treated than in untreated patients (p = 0.01 and 0.07). There were no significant differences with respect to response to treatment, but a higher number of P-gp molecules was found in non-responders. When the results of the functional test were put together with the quantification assay this allowed the detection of 71% non-responders. Our findings suggest that quantification of the P-gp could be of value in the assessment of possible drug resistance in CLL.
Maynadié
M
M
Academic Department of Haematology and Cytogenetics, Royal Marsden NHS Trust, London, U.K.
Matutes
E
E
Catovsky
D
D
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000097:blood* / Q000276:immunology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000276:immunology; D001692:Biological Transport / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D005260:Female; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000097:blood* / Q000276:immunology; D009439:Neuraminidase / Q000494:pharmacology; D020112:Rhodamine 123; D012235:Rhodamines; D012680:Sensitivity and Specificity; D014700:Verapamil / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D000911:Antibodies, Monoclonal; D002121:Calcium Channel Blockers; D005456:Fluorescent Dyes; D009363:Neoplasm Proteins; D012235:Rhodamines; D020112:Rhodamine 123; D004317:Doxorubicin; D014700:Verapamil; D009439:Neuraminidase