THROMBOPOIETIN AND ITS RECEPTOR

Thrombopoietin (TPO), the primary physiological regulator of platelet production, was initially thought to be a lineage-specific factor acti ng predominantly on megakaryocytopoiesis. Detailed studies establish t hat this cytokine mediates biological effects on a broad spectrum of h ematopoietic progenitor cells, including stem cells. TPO is a hormone constitutively produced mainly by the liver and kidney. Plasma TPO lev els are regulated by the platelet and megakaryocyte mass through Mpl r eceptor binding, internalization and degradation. The Mpl receptor is a member of the hematopoietin receptor superfamily lacking intrinsic k inase activity, Upon ligand-induced Mpl homodimerization, the major si gnaling events for proliferation are mediated through the JAK2/STAT5 p athway, while differentiation might occur through a prolonged activati on of the MAPK pathway. Preclinical and clinical studies demonstrate t he potential use of TPO in a variety of contexts, but it is too early to evaluate its benefit in reducing platelet transfusion.