RALBP1/RLIP76 mediates multidrug resistance.

RLIP76/RALBP1 is a multi-specific drug-transporter which can mediate drug-resistance in lung and other cancers, but its ability to mediate multidrug-resistance has not been previously demonstrated in hematological malignancy. Present studies in K562 human myelogenous leukemia show that RALBP1 overexpression confers broad resistance to multiple chemotherapy drugs including cisplatin, melphalan, doxorubicin, daunorubicin, vincristine, vinblastine, vinorelbine, and mitomycin-C. Conversely, inhibition of RALBP1 by polyclonal antibodies causes increased drug-accumulation and increased cytotoxicity. These studies demonstrate the potential utility of targeting RALBP1 in the treatment of leukemia.