DIFFERENTIATION AND MULTIDRUG-RESISTANCE IN RESPONSE TO DRUG-TREATMENT IN THE K562-HUMAN LEUKEMIA-CELL LINE

The relationship between differentiation and P-glycoprotein expression in response to chemotherapeutic drugs was studied in the K562 human l eukaemia cell line by treatment with low, but clinically achievable le vels of vinblastine and epirubicin. Resistant sublines were easily gen erated with the multidrug resistant phenotype being expressed in respo nse to drug treatment as low as 1 ng/ml vinblastine and 10 ng/ml epiru bicin. These sublines showed stable but heterogeneous expression of P- glycoprotein as revealed by immunocytochemistry, and confirmed by clon ing. This heterogeneity was maintained over 18 months with intermitten t drug treatment. While selection for resistance induced erythroid and myeloid differentiation, expression of P-glycoprotein was not correla ted with the stem cell antigen CD34 or with specific markers of erythr oid or myeloid differentiation.