Oncogenes and erythroid differentiation.

Committed erythroid progenitors are the cellular targets of oncogene-carrying avian and murine retroviruses that induce acute erythroleukemia. Normally, these cells undergo a fixed program of 5-10 cell divisions while terminally differentiating into erythrocytes. The sustained self-renewal observed in the context of their retrovirus-mediated leukemic transformation has been viewed as an abnormal, oncogene-induced effect. Recently, however, it was found that certain combinations of growth/differentiation hormones (e.g. TGF-alpha and estradiol) can induce normal avian erythroid progenitors to undergo a similarly extensive self-renewal as caused by oncogenes. This leads to the hypothesis that leukemia-inducing oncogenes take advantage of the committed erythroid progenitors' capacity for self-renewal rather than reprogramming their targets to abnormal growth, as suspected previously. These findings and their implications will be discussed.