title: 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 microM 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 microM 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.
authors.affiliation: Hematology-Oncology and Clinical Cancer Chemotherapy Division, National Cancer Center Hospital, Tokyo.
authors.forename: Y
authors.initials: Y
authors.lastname: Ishida
authors.forename: T
authors.initials: T
authors.lastname: Ohtsu
authors.forename: H
authors.initials: H
authors.lastname: Hamada
authors.forename: Y
authors.initials: Y
authors.lastname: Sugimoto
authors.forename: K
authors.initials: K
authors.lastname: Tobinai
authors.forename: K
authors.initials: K
authors.lastname: Minato
authors.forename: T
authors.initials: T
authors.lastname: Tsuruo
authors.forename: M
authors.initials: M
authors.lastname: Shimoyama
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal; D003609:Dactinomycin / Q000627:therapeutic use; D003630:Daunorubicin / Q000627:therapeutic use; D004317:Doxorubicin / Q000627:therapeutic use; D004351:Drug Resistance; D005047:Etoposide / Q000627:therapeutic use; D015870:Gene Expression; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000378:metabolism; D008223:Lymphoma / Q000032:analysis / Q000188:drug therapy*; D008562:Membrane Glycoproteins / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D008942:Mitoxantrone / Q000627:therapeutic use; D012333:RNA, Messenger / Q000235:genetics; D014407:Tumor Cells, Cultured; D014747:Vinblastine / Q000627:therapeutic use; D014750:Vincristine / Q000627:therapeutic use; D014751:Vindesine / Q000627:therapeutic use
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D003609:Dactinomycin; D014750:Vincristine; D014747:Vinblastine; D005047:Etoposide; D004317:Doxorubicin; D008942:Mitoxantrone; D014751:Vindesine; D003630:Daunorubicin