Inhibition by dexamethasone of commitment to erythroid differentiation in murine erythroleukemia cells

Abstract

The inhibition of erythroid differentiation of murine erythroleukemia cells by dexamethasone (DEX) has been investigated on a clonal basis. At concentrations which had no detectable effect on cell proliferation, DEX3 rapidly inhibited the dimethyl sulfoxide (DMSO)-induced commitment of individual murine erythroleukemia cells to the differentiation program. DEX did not prevent heme accumulation in cells already committed to the differentiation process. The rate of globin messenger RNA (mRNA) synthesis was reduced in cells treated with DMSO and DEX compared to cells treated with DMSO alone. The reduction in the rate of globin mRNA synthesis was proportional to the reduction caused by DEX in the rate of commitment. DEX inhibition in the rate of commitment and of globin mRNA synthesis of DMSO-treated cells was reversible. Upon removal of DEX, continued DMSO treatment resulted in a rapid increase in both the rate of globin mRNA synthesis and the rate of commitment. The rate of globin mRNA synthesis after DEX release was also proportional to the rate of commitment. These results suggest that DEX exerts an inhibitory effect on heme and globin synthesis by blocking commitment to terminal erythroid differentiation.