Regulation of differentiation in normal and transformed erythroid cells

Summary Studies are described employing two erythropoietic systems to elucidate regulatory mechanisms that control both normal erythropoiesis and erythroid differentiation of transformed hemopoietic precursors. Evidence is provided suggesting that normal erythroid cell precursors require erythropoietin as a growth factor that regulates the number of precursors capable of differentiating. Murine erythroleukemia cells proliferate without need of erythropoietin; they show a variable, generally low, rate of spontaneous differentiation and a brisk rate of erythropoiesis in response to a variety of chemical agents. Present studies suggest that these chemical inducers initiate a series of events including cell surface related changes, alterations in cell cycle kinetics, and modifications of chromatin and DNA structure which result in the irreversible commitment of these leukemia cells to erythroid differentiation and the synthesis of red-cell-specific products. Presented in the formal symposium on Mechanisms of Cellular Control at the 28th Annual Meeting of the Tissue Culture Association, New Orleans, Louisiana, June 6–9, 1977. These studies were supported in part by grants and contracts from the National Institutes of Health (GM-14552, CA-13696, CA-18314, NO1-CB-4008 and NO1-CP-1008) and the National Science Foundation (NSF-PCM-75-08696). E.F. and R.C.R. are fellows of the Schultz Foundation; A.B. was supported in part as an American Cancer Society Scholar; J.E.S. was supported by a USPHS Medical Scientist Training Grant; and M.T. and G.M.M. are Hirschl Trust Scholars.