[Thrombopoietin and megakaryocyte differentiation].
Regulation of megakaryocytopoiesis and platelet production is a complex phenomenon. It has been demonstrated that numerous pleiotropic cytokines act in vivo and in vitro on megakaryocytopoiesis. Historically, studies on the regulation of megakaryocytopoiesis were largely dominated by the concept of humoral regulation. Despite 35 years of work, the factor responsible for these effects (thrombopoietin, TPO) could not be purified to homogeneity. The proto-oncogene c-mpl has been demonstrated to encode a protein which is the receptor for a humoral cytokine regulating megakaryocytopoiesis. Its ligand was isolated by three independent groups. The purified protein was termed Mpl-L (Mpl-Ligand), thrombopoietin (TPO), or megakaryocyte growth and development factor (MGDF). Strong evidence that Mpl-L is the homeostatic regulator of platelet production has been provided by c-mpl or Mpl-L knock-out mice which have a severe but not lethal thrombocytopenia. In vitro experiments have indicated that the Mpl-L acts both as a proliferative and differentiative factor as many other CSF. At the unicellular level, Mpl-L acts on MK progenitors inducing their proliferation. Mpl-L induces polyploidisation of the MKs and cytoplasmic maturation leading to an in vitro platelet production. As a single cytokine Mpl-L is the most potent growth factor for the MK lineage in vitro. However, a combination of cytokines can totally replace the effects of Mpl-L both on proliferation of MK progenitors and their maturation. In addition, Mpl-L has a major effect on primitive hematopoietic progenitors.
Vainchenker
W
W
INSERM U 362, PR1, Institut Gustave Roussy, Villejuif, France.
Debili
N
N
Norol
F
F
Wendling
F
F
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D015870:Gene Expression / Q000502:physiology; D006410:Hematopoiesis / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008533:Megakaryocytes / Q000166:cytology*; D051379:Mice; D018345:Mice, Knockout; D000090063:Proto-Oncogene Mas
Thrombopoïétine et différenciation mégacaryocytaire.