ICGM/Inserm U. 363, hôpital Cochin, 27, rue du Faubourg-Saint-Jacques, 75014 Paris.
Cytokine signaling through the Jak/Stat pathway has been shown to play a crucial role in hematopoietic cell proliferation, survival and differentiation. In addition constitutive activity of the Jak/Stat pathway has been described in cells from leukemic patients or in hematopoietic cells transformed by various viral or cellular oncogenes indicating that inappropriate activation of this pathway could be one of the events that contribute to leukemogenesis. Constitutive activity of the Jak/Stat pathway may result from the expression of oncogenic fusion proteins involving the Jak2 or Stat5B described in different types of leukemia or through the activity of viral or cellular oncogenes. Genetic manipulations of the jak and stat genes in vitro and in vivo have shown that both proteins regulate expression of genes involved in cell survival and cell cycle. The aim of this review is to summarize the current knowledge on the role of this signaling pathway in hematopoiesis and leukemogenesis. Mice with inactivated jak and stat genes are now available and will be helpful in the future to determine the functional importance of this pathway in cell transformation.