INHIBITION OF THE DIFFERENTIATION OF HUMAN MYELOID CELL-LINES BY REDOX CHANGES INDUCED THROUGH GLUTATHIONE DEPLETION

We have investigated the effect of redox changes in vivo on the differ entiation of two human myeloid cell lines, HL-60 and KG-1. The glutath ione-depleting agent diethyl maleate (DEM) prevented the development o f differentiated features in response to phorbol esters, including adh erence of the cells to plastic surfaces and repression of the myeloper oxidase and CD34 genes. Moreover, DEM abolished phorbol 12-myristate 1 3-acetate-induced activation of the transcription factors AP-1 and Egr -1, suggesting that inhibition of differentiation may be due, at least in part, to redox modifications of these proteins.