N-(4-HYDROXYPHENYL)RETINAMIDE INDUCES APOPTOSIS IN T-LYMPHOMA AND T-LYMPHOBLASTOID LEUKEMIA-CELLS

We demonstrate that N-(4-hydroxyphenyl)-all-trans-retinamide (4-HPR), a synthetic retinoic acid (RA) derivative, is a potent and selective i nducer of apoptosis in malignant T lymphoid cells, but has little effe ct on normal lymphoid cells of the thymus or spleen. 4-HPR and its ste reoisomer, 9-cis-4-HPR, are 50 to >150 times more potent than 7 other retinoids in killing CEM-C7 human T lymphoblastoid leukemia cells and P1798-C7 murine T lymphoma cells. 4-HPR's apoptotic action requires th e intact molecule bearing both the retinoid moiety and the hydroxyphen ol ring; 4-HPR remains unmetabolized after uptake into CEM-C7 and P179 8-C7 cells for up to 24 hours. We also show that glucocorticoid (GC)-r esistant variants are equally susceptible to 4-HPR as are GC-sensitive cells. Thus, 4-HPR may be potentially important as a new chemotherape utic drug for use as alternative to, or in combination with, conventio nal drugs for treating lymphoid malignancies.