Thrombopoietin: a tool for understanding thrombopoiesis.

Although first proposed to be the primary regulator of platelet production 45 years ago, the gene for thrombopoietin was cloned only within the last decade. Since then, our understanding of megakaryocyte and platelet production has increased substantially, and it is now appreciated that in addition to its critical role in regulating thrombopoiesis, the hormone affects multiple aspects of hematopoiesis, including playing a non-redundant role in stem cell survival, self-renewal and expansion. In addition to this greater physiological understanding of thrombopoietin biology, the molecular mechanisms by which the hormone affects cell survival and proliferation are coming under increased scrutiny. At least four signaling pathways have been identified that play important and non-overlapping roles in stem cell and megakaryocyte growth and development, potentially providing new strategies to therapeutically intervene in hematopoiesis. This review will focus on our current understanding of these processes.