EFFECTS OF 1-BETA-D-ARABINOFURANOSYLCYTOSINE AND PHORBOL ESTER ON DIFFERENTIATION OF HUMAN K562 ERYTHROLEUKEMIA-CELLS

Abstract
1-.beta.-D-arabinofuranosylcytosine (ara-C) induces Hb synthesis in human K562 erythroleukemia cells. The present study demonstrates that ara-C treatment of K562 cells results in both increased heme synthesis and accumulation of .alpha.-, .gamma., .epsilon.-, and .zeta.-globin RNA. The results also demonstrate that ara-C enhances K562 cell surface expression of glycophorin. Phorbol ester (12-O-tetradecanoylphorbol-13-acetate; TPA) inhibits the effects of ara-C on heme production, accumulation of globin RNA and glycophorin expression. The inhibitory effect occurs maximally when K562 cells are treated with TPA before undergoing ara-C-induced commitment to erythroid differentiation. TPA probably inhibits an early step in the process required for ara-C to enhance expression of genes involved in the erythroid program.