Multidrug resistance in cultured human leukemia and lymphoma cell lines detected by a monoclonal antibody, MRK16.

Abstract

Forty cultured human leukemia and lymphoma cell lines never exposed to anticancer agents in culture, apart from doxorubicin (ADM)‐resistant K562/ADM, were examined for reactivity with a monoclonal antibody, MRK16 in F(ab′)2 form [MRK16‐F(ab′)2], which recognizes P‐glycoprotein (P‐gp). The relative resistance index to various drugs was calculated by dividing the 50% growth inhibitory concentration (IC50) of the test cell line by IC50 of K562, which was the negative control in the antibody experiment. MRK16‐F(ab′)2 reacted with four cell lines, K562/ADM, KYO‐1, HEL and CMK, which had relative resistance index values of 2 or more to vincristine (VCR), vindesine, vinblastine, ADM, daunorubicin, mitoxantrone (MIT), etoposide (VP‐16) and actinomycin‐D (ACT‐D). The level of resistance to VCR and ADM in these cell lines decreased significantly in the presence of 10 μM verapamil in vitro. Significant expression of mRNA of P‐gp gene was also detected in K562/ADM, KYO‐1 and HEL. MRK16‐F(ab′)2 did not react with 36 other cell lines. Among them, three cell lines, PL‐21, P31/FUJ and KOPM‐28, had relative resistance index values of 2 or more to anthracyclines, MIT and VP‐16, but not to vinca alkaloids or ACT‐D. The level of ADM‐resistance in these cell lines did not decrease significantly in the presence of 10 μM verapamil. Five cell lines, ATL‐1K, HL‐60, KMOE‐2, ML‐1 and U266, had relative resistance index values of 2 or more to some of the drugs, but not to the others, and 19 other cell lines did not. These results indicate that the reactivity of MRK16‐F(ab′)2 correlates with a relative resistance index of 2 or more to all these drugs in cultured human leukemia and lymphoma cell lines.