DIFFERENTIATION EFFECT OF ACYCLIC RETINOID ON ACUTE PROMYELOCYTIC LEUKEMIA-CELLS

Acyclic retinoid (all-trans-3, 7, 11, 15-tetramethyl-2, 4, 6, 10, 14-h exadecapentaenoic acid) binds cellular retinoic acid-binding protein w ith an affinity similar to that of all-trans retinoic acid and induces differentiation of human hepatoma cell lines and a human acute myelog enous leukemia cell line (HL-60). We investigated the in vitro efficac y of acyclic retinoid to induce the differentiation of acute promyeloc ytic leukemia (APL) cells using primary cultured cells obtained from 1 1 APL patients. Five days' incubation with acyclic retinoid effected a dose-dependent induction of differentiation. Cells from eight patient s showed maximum differentiation at 10(-6) M acyclic retinoid. Cells f rom one patient required 10(-5) M for maximum differentiation, while t hose from two patients exhibited moderate differentiation at 10(-5) M. Five days' incubation with acyclic retinoid (10(-7) - 10(-5) M) did n ot affect the viability or number of cells from any patient except one , whose cells showed a slight decrease in viability at 10(-5) M. Thus, we conclude that acyclic retinoid induced the differentiation of prim ary cultured APL cells at concentrations of 10(-6) - 10(-5) M, a range at which it is not toxic.