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) came with the molecular cloning and characterization of the in vitro and in vivo properties of the c-Mpl ligand. Gene targeting experiments have demonstrated that the TPO/Mpl receptor signalling pathway is the principal physiological regulator of megakaryocytes and platelets. Analysis of signalling through c-Mpl has provided important insights into the function of this pathway, which, as with other members of the hemopoietin receptor family, involves activation of the JAK/STAT and Ras signalling cascades. Preclinical studies have documented a role for this molecule in overcoming thrombocytopenia following chemo/radiotherapy in several animal models. Clinical studies have demonstrated the safety and efficacy of Mpl ligand in elevating platelet counts. The identification of thrombopoietin has provided an important impetus in understanding megakaryocyte and platelet physiology, and provided a new therapeutic that will find application in a variety of clinical contexts.
Alexander
W S
WS
Walter and Eliza Hall Institute of Medical Research, Victoria, Australia.
Begley
C G
CG
D001792:Blood Platelets / Q000378:metabolism*; D006801:Humans; D008533:Megakaryocytes / Q000378:metabolism*; D009363:Neoplasm Proteins; D011092:Polyethylene Glycols / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction; D013234:Stem Cells; D013926:Thrombopoietin / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology
D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; D011994:Recombinant Proteins; C103117:polyethylene glycol-recombinant human megakaryocyte growth and development factor; C082218:MPL protein, human; D011092:Polyethylene Glycols; D013926:Thrombopoietin