Atypical Multiple Drug Resistance in a Human Leukemic Cell Line Selected for Resistance to Teniposide (VM-26)1

Resistance to the cytotoxic effects of many natural product drugs after exposure to a single agent is a common observation. The classes of drugs included in the "classic" multiple drug resistance phenotype are Vinca alkaloids, anthracyclines, epipodophyllotoxins, and antibiotics. We re port here the characterization of a human leukemic cell line (CEM/VM1) with "atypical" multiple drug resistance: despite resistance and crossresistance to etoposide, anthracyclines, mitoxantrone, and 4'-((9-acridinyl)amino)methanesulphon-in-anisidide (mA.MSA), these cells retain sensitivity to the Vinca alkaloids. Further, even though this cell line is »40-foldcross-resistant to the cytotoxic effect of etoposide (VP-16), it is similar to drug-sensitive CEM cells in the cellular pharmacology of [3H)VP-16 as determined by zero time binding, initial influx rate, steady state drug concentration, and unidirectional efflux. Our studies suggest that the resistance of CEM/VM-1 cells to epipodophyllotoxins is due to an altered interaction between drug and its cellular target(s) by a mech anism unrelated to the decreased cellular concentration of drug associated with the "classic" multiple drug resistance phenotype.