Evolution of a mutant J2E erythroid cell line which does not respond to erythropoietin

The recently derived J2E cell lines differentiate in response to erythropoietin. However, during the course of growth in culture, a subclone has emerged which fails to synthesize hemoglobin or show accelerated proliferation following hormonal stimulation. The inability to respond to erythropoietin is not due to autocrine production of the hormone by these cells. Moreover, it appears unlikely that the block occurs at the level of the erythropoietin receptor as the number of receptors per cell was only marginally reduced and both ligand binding and internalization were normal. It is likely, therefore, that the intracellular signal transduction mechanism is faulty or a defect in hemoglobin production has developed.