POSSIBLE ROLES OF AN ADULT T-CELL LEUKEMIA (ATL)-DERIVED FACTOR THIOREDOXIN IN THE DRUG-RESISTANCE OF ATL TO ADRIAMYCIN

Chemotherapy for adult T-cell leukemia (ATL) has been reported to fail to induce complete remission because of drug resistance in most patie nts. We have examined the expression of an ATL-derived factor (ADF)/th ioredoxin in relation to resistance to adriamycin (ADM) in various T-c ell leukemia cell lines including ATL cell lines, Immunoblot analysis demonstrated that ATL cell lines expressed ADF/thioredoxin at levels 2 .8 to 12 times those of other T-cell acute lymphocytic leukemia (T-ALL ) cell lines, and that ATL cell lines were 2 to 15 times more resistan t to ADM than other T-ALL cell lines, Therefore, we established ADM-re sistant cell lines from three different ATL cell lines, and examined t he correlation between ADM resistance and expression of ADF/thioredoxi n. ADM-resistant ATL cell lines were also found to be resistant to oth er drugs such as cisplatin and etoposide, and they expressed ADF/thior edoxin at levels 5 to 10 times those of parent ATL cell lines, Diamide and sodium selenite, which have been reported to inhibit ADF/thioredo xin, restored the sensitivity to ADM in ATL and ADM-resistant ATL cell lines, The MDR-1 gene product, a membrane P-glycoprotein (Pgp), was n ot expressed on ATL cell lines or ADM-resistant ATL cell lines, Topois omerase II and glutathione peroxidase activities in T-cell leukemia ce ll lines were not correlated with ADM resistance, These results sugges t that ADF/thioredoxin may play an important role in the drug resistan ce of ATL cells to ADM. (C) 1997 by The American Society of Hematology .