[Megakaryopoiesis: regulation of platelet production by thrombopoietin]

Each day, 2x10(11) platelets are produced in the human body by a highly regulated mechanism. The biology of platelet formation is unique, as platelets arise from cytoplasmic fragmentation of their marrow precursor, the megakaryocyte (MK). MKs are giant cells that undergo polyploidisation during maturation, through a process called endomitosis leading to a cell with a 2(x)N DNA content. This huge size allows each MK to produce several thousand platelets. MK cytoplasmic fragmentation is a dynamic and organized process beginning with extensions, called proplatelets, that further fragment to give rise to platelets. This last process takes place in the bloodstream and is regulated by shear stress. Thrombopoietin (TPO) is the hormone that, with the exception of platelet shedding, regulates all the steps of megakaryopoiesis, from the hematopoietic stem cell to MK maturation. TPO is mostly synthesized by the liver, mainly in constitutive fashion, and its plasma level is dependent on its clearance by platelets and MK after binding to its receptor MPL. MPL is a type I homodimeric cytokine receptor that requires the kinase JAK2 for its signaling activity. MPL and JAK2 are involved in numerous inherited and malignant disorders leading to thrombocytopenia and aplastic anemia or to thrombocytosis. They are now being targeted therapeutically.