Multidrug Resistance in Cultured Human Leukemia and Lymphoma Cell Lines Detected by a Monoclonal Antibody, MRK16

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 μ M 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 μ M 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.