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.
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Walter and Eliza Hall Institute of Medical Research, P.O. Royal Melbourne Hospital, Victoria, Australia.
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D015672:Erythroid Precursor Cells / Q000166:cytology* / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D006133:Growth Substances / Q000502:physiology; D006801:Humans; D009857:Oncogenes; D016211:Transforming Growth Factor alpha / Q000494:pharmacology
D006133:Growth Substances; D016211:Transforming Growth Factor alpha; D004958:Estradiol