THROMBOPOIETIN IN-VITRO AND IN-VIVO

The characterization of the c-Mpl receptor resulted from studies on a murine retrovirus, and proved an important step in the Identification of a key hemopoietic regulator. First proposed and named in 1958, the ultimate characterization of the long-awaited 'thrombopoietin' (TPO) c ame with the molecular cloning and characterization of the in vitro an d in vivo properties of the c-Mpl ligand. Gene targeting experiments h ave demonstrated that the TPO/Mpl receptor signalling pathway is the p rincipal physiological regulator of megakaryocytes and platelets. Anal ysis of signalling through c-Mpl has provided important insights into the function of this pathway, which, as with other members of the hemo poietin receptor family, involves activation of the JAK/STAT and Ras s ignalling cascades. Preclinical studies have documented a role for thi s molecule in overcoming thrombocytopenia following chemo/radiotherapy in several animal models. Clinical studies have demonstrated the safe ty and efficacy of Mpl ligand in elevating platelet counts. The identi fication of thrombopoietin has provided an important impetus in unders tanding megakaryocyte and platelet physiology, and provided a new ther apeutic that will find application in a variety of clinical contexts.