Erythroleukemia cells: variants inducible for hemoglobin synthesis without commitment to terminal cell division

Abstract

Murine erythroleukemia cells (MELC) are virus-transformed erythroid precursors that appear to be blocked at an erythroid precursor stage comparable to the erythroid colony-forming unit (CFU-e). These cells are useful in examining factors regulating terminal differentiation. Induced MELC are characterized by a coordinated program of gene expression, including commitment to terminal cell division, accumulation of globin mRNAs and corresponding hemoglobins, and accumulation of several other proteins, including the chromatin-associated protein H1(0). Two cloned variant cell lines, DR10 and R1, have been developed from inducer-sensitive DS19 cells by selection for inducer resistance. DR10 and R1 cells fail to display commitment to terminal cell division when cultured with dimethyl sulfoxide (Me2SO), hexamethylene bisacetamide (HMBA), or butyric acid. Both cell lines are induced by all three agents to accumulate H1(0). DR10 cells are resistant to Me2SO-mediated accumulation of hemoglobin but are sensitive to HMBA- or butyric acid-mediated accumulation. R1 cells are resistant to Me2SO- and HMBA-mediated accumulation of hemoglobin but are sensitive to butyric acid-mediated accumulation. Both DR10 and R1 are commitment-negative MELC variants, displaying variable responses to inducers with respect to other features of terminal erythroid cell differentiation.