Expression of the multiple drug resistance gene (mdr-1) and epitope masking in chronic lymphatic leukaemia.
Resistance to cytotoxic agents is a common clinical problem in the treatment of chronic lymphatic leukaemia (CLL). The multidrug resistant (MDR) phenotype characterized by increased levels of a specific cell membrane p-glycoprotein, confers cross resistance to a wide range of structurally dissimilar antineoplastic drugs. We have studied the expression of this p-glycoprotein in chronic lymphatic leukaemia measured by immunofluorescence using a monoclonal antibody MRK 16 by flow cytometry. Initial results showed that only 12% of lymphocyte samples from CLL patients showed increased p-glycoprotein, conflicting with a previous observation that 53% of CLL patients had an increased level of mdr-1 mRNA. Treatment of the cells with neuraminidase to remove sialic acid residues increased the proportion of patients showing increased p-glycoprotein to 52%. This suggest that in a subset of CLL patients post translational modification of the protein occurs masking the epitope recognized by MRK 16. Abnormal sialylation patterns associated with malignancy are a well-recognized phenomenon.
Cumber
P M
PM
Department of Haematology, University of Wales College of Medicine, Cardiff.
Jacobs
A
A
Hoy
T
T
Fisher
J
J
Whittaker
J A
JA
Tsuruo
T
T
Padua
R A
RA
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000032:analysis; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002460:Cell Line; D002699:Chlorambucil / Q000627:therapeutic use; D004351:Drug Resistance / Q000235:genetics*; D000939:Epitopes / Q000032:analysis; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology; D008562:Membrane Glycoproteins / Q000032:analysis* / Q000235:genetics; D009439:Neuraminidase / Q000494:pharmacology; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics; D012016:Reference Values; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D014158:Transcription, Genetic
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000939:Epitopes; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D002699:Chlorambucil; D009439:Neuraminidase