Anticancer Drugs Overexpress Fas-associated Phosphatase-1 in Some Leukemic Cells

To evaluate the involvement between Fasassociated phosphatase-1 (FAP-1) and drug resistance, the expression of FAP-1 in leukemic cell lines, drugresistant sublines, and leukemic cells was examined by RT-PCR. In comparison with the parental cell line (KY-821), arabinofuranosylcytosine (ara-C)-resistant subline (KY-Ra), and vincristine (VCR)-resistant subline (KY-VCR) showed an increase in FAP-1 expression and resistance to anti-CD95 antibody-induced apoptosis. Leukemic cell lines (KY-821 and Jurkat) revealed an increase in FAP-1 expression after exposure to ara-C (1×10^<-5>M) and VCR (1×10^<-7>M). Furthermore, after exposure to anticancer drugs at low dosages for five days, both KY-821 and Jurkat revealed an increase in FAP-1 expression and resistance to anti-CD95 antibody-induced apoptosis. In study with de novo leukemic cells, two cases showed an increase in FAP-1 expression after exposure to anticancer drugs, of which one revealed an increased resistance to anti-CD95 antibody-induced apoptosis. These results indicate a close involvement between CD95-mediated apoptosis and drug resistance, and suggest that anticancer drugs suppress CD95-mediated apoptosis in part by inducing FAP-1 overexpression in some leukemic cells.