Differentiation and multidrug resistance in response to drug treatment in the K562 human leukaemia cell line.
The relationship between differentiation and P-glycoprotein expression in response to chemotherapeutic drugs was studied in the K562 human leukaemia cell line by treatment with low, but clinically achievable levels of vinblastine and epirubicin. Resistant sublines were easily generated with the multidrug resistant phenotype being expressed in response to drug treatment as low as 1 ng/ml vinblastine and 10 ng/ml epirubicin. These sublines showed stable but heterogeneous expression of P-glycoprotein as revealed by immunocytochemistry, and confirmed by cloning. This heterogeneity was maintained over 18 months with intermittent drug treatment. While selection for resistance induced erythroid and myeloid differentiation, expression of P-glycoprotein was not correlated with the stem cell antigen CD34 or with specific markers of erythroid or myeloid differentiation.
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Neurobiology Unit, School of Biological and Biomedical Sciences, University of Technology, Sydney, N.S.W., Australia.
Davey
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Davey
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Kidman
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D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000951:Antigens, Neoplasm / Q000032:analysis; D015153:Blotting, Western; D002352:Carrier Proteins / Q000032:analysis / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D004351:Drug Resistance; D015251:Epirubicin / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000032:analysis / Q000187:drug effects*; D009363:Neoplasm Proteins / Q000032:analysis / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D014700:Verapamil / Q000494:pharmacology; D014747:Vinblastine / Q000494:pharmacology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000951:Antigens, Neoplasm; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D015251:Epirubicin; D014747:Vinblastine; D014700:Verapamil