A novel multidrug resistance in cultured leukemia and lymphoma cells detected by a monoclonal antibody to 85-kDa protein, MRK20.
A monoclonal antibody, MRK20, in F(ab')2 form [MRK20-F(ab')2], which reacts with 85-kDa membrane protein in a doxorubicin (ADM)-resistant subline (K562/ADM) of human myelogenous leukemia cell line, K562, was examined for reactivity with 41 cultured human leukemia and lymphoma cell lines. None of these cell lines had ever been exposed to any anticancer agent in vitro except K562/ADM. 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 (the negative control in the antibody experiment). MRK20-F(ab')2 reacted with seven cell lines, KYO-1 derived from chronic myelogenous leukemia in blastic crisis (CMLbc), CMK from acute megakaryoblastic leukemia, HEL from erythroleukemia, P31/FUJ from acute monocytic leukemia, KOPM-28 from CMLbc, PL-21 from acute promyelocytic leukemia and K562/ADM. MRK20-F(ab')2 did not react with 34 other cell lines. All seven MRK20-F(ab')2-positive cell lines had relative resistance index values of 2 or more to anthracyclines (ADM, pyrarubicin, daunorubicin), mitoxantrone, etoposide, bleomycin, and pepleomycin. There was no distinct correlation between the reactivity to MRK20-F(ab')2 and a higher relative resistance index than 2 to vinca alkaloids, actinomycin-D, cisplatin, 4-hydroperoxycyclophosphamide, nimustine hydrochloride, methotrexate or cytarabine. These results indicate that MRK20-F(ab')2 detects a novel multidrug resistance to anthracyclines, mitoxantrone, etoposide, bleomycin and pepleomycin in cultured human leukemia and lymphoma cells.
Ohtsu
T
T
Hematology-Oncology and Clinical Cancer Chemotherapy Division, National Cancer Center Hospital, Tokyo.
Ishida
Y
Y
Tobinai
K
K
Minato
K
K
Hamada
H
H
Ohkochi
E
E
Tsuruo
T
T
Shimoyama
M
M
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000911:Antibodies, Monoclonal; D004351:Drug Resistance; D006801:Humans; D007140:Immunoglobulin Fab Fragments; D007938:Leukemia / Q000378:metabolism* / Q000473:pathology; D008223:Lymphoma / Q000378:metabolism* / Q000473:pathology; D008565:Membrane Proteins / Q000032:analysis* / Q000276:immunology / Q000502:physiology; D008942:Mitoxantrone / Q000494:pharmacology; D014748:Vinca Alkaloids / Q000494:pharmacology
D000903:Antibiotics, Antineoplastic; D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D008565:Membrane Proteins; D014748:Vinca Alkaloids; D008942:Mitoxantrone