Emergence of myeloid cells from cultures of J2E erythroid cells is linked with karyotypic abnormalities

Abstract

J2E cells are an erythroid cell line immortalized at the proerythroblast stage of differentiation by the J2 retrovirus which contains the raf and myc oncogenes. In response to erythropoietin, these cells terminally differentiate into mature, hemoglobin-producing erythroid cells. We have shown previously that B cells overexpressing raf and myc acquired the phenotype of macrophages, and here we demonstrate that, under adverse growth conditions, myeloid cells can also emerge from J2E cultures. Morphologically, ultrastructurally, and by cytochemical analyses, these cells resembled monocytic precursor cells at different stages of differentiation. They no longer responded to erythropoietin, failed to express an erythroid-specific surface antigen, and ceased producing transcripts for globin genes, GATA-1 and SCL. Most of the converted cells displayed surface antigens typically found on myeloid cells and in vivo produced histiocytomas with severe cachexia, instead of erythroleukemias. All of the myeloid convertants had karyotypic abnormalities, and we speculate that these mutations may have triggered the transition from erythroid to myeloid phenotype. Overexpression of raf and myc oncogenes may have generated genetic instability, which then influenced the commitment of cells to specific lineages.