DIFFERENTIAL EXPRESSION AND ACTIVITY OF P-GLYCOPROTEIN AND MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN IN CD34-POSITIVE KG1A LEUKEMIC-CELLS

CD34(+) acute myeloid leukemias generally respond poorly to chemothera py when compared to CD34(-) myeloid leukemias. In order to contribute to the analysis of the mechanisms involved in this drug resistance, ex pression and activity of P-glycoprotein (P-gp) and multidrug resistanc e-associated protein (MRP), two drug efflux pumps conferring multidrug resistance, have been investigated in the CD34(+) KG1a leukemic myelo id cell line and in two CD34(-) K562 and HL60 leukemic myeloid cell li nes. Reverse transcription-polymerase chain reaction and dye efflux as says revealed that KG1a cells express P-gp but not MRP whereas neither P-gp nor MRP were detected in K562 and HL60 cells. In addition, KG1a cells were demonstrated to display resistance to anticancer drug subst racts for P-gp such as vincristine and daunorubicin and to poorly accu mulate vincristine. These results indicated that P-gp, in contrast to MRP, is expressed and functional in the drug-resistant CD34(+) KG1a ce ll line. that may constitute a useful cellular model to analyze the co nstitutive chemoresistance of CD34(+) acute myeloid leukemias.