Increased drug accumulation ex vivo with cyclosporin in chronic lymphatic leukemia and its relationship to epitope masking of P-glycoprotein.
The ability of cyclosporin to modify drug accumulation in vitro, measured by the cellular accumulation of daunorubicin, was examined. In 42 patients with chronic lymphatic leukaemia this correlates well with the levels of P-glycoprotein (Pgp) measured by immunofluorescent labelling of Pgp after treatment of the cells with neuraminidase to unmask the epitope recognized by the monoclonal antibody MRK 16. It is shown that flow cytometric analysis using MRK 16 to detect Pgp expression levels together with drug accumulation studies can rapidly assess the multidrug-resistant phenotype of patients' cells, and enable selection of those suitable for therapy with agents known to circumvent mdr-1 mediated drug resistance.
Cumber
P M
PM
Department of Haematology, University of Wales College of Medicine, Cardiff, UK.
Jacobs
A
A
Hoy
T
T
Whittaker
J A
JA
Tsuruo
T
T
Padua
R A
RA
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D001692:Biological Transport / Q000187:drug effects; D002699:Chlorambucil / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology*; D003630:Daunorubicin / Q000378:metabolism; D004351:Drug Resistance; D006801:Humans; D066298:In Vitro Techniques; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000276:immunology*; D009439:Neuraminidase / Q000494:pharmacology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D008562:Membrane Glycoproteins; D002699:Chlorambucil; D016572:Cyclosporine; D009439:Neuraminidase; D003630:Daunorubicin