Thrombopoietin in vitro and in vivo
Details
Publication Year 1998-03,Volume 4,Issue #1,Page 25-34
Journal Title
CYTOKINES CELLULAR & MOLECULAR THERAPY
Publication Type
Journal Article
Abstract
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.
Publisher
MARTIN DUNITZ LTD
Keywords
C-MPL LIGAND; HUMAN MEGAKARYOCYTE GROWTH; COLONY-STIMULATING FACTOR; MYELOPROLIFERATIVE LEUKEMIA-VIRUS; PROTEIN-TYROSINE PHOSPHORYLATION; RECOMBINANT HUMAN THROMBOPOIETIN; BONE-MARROW TRANSPLANTATION; HEMATOPOIETIC STEM-CELLS; BLOOD PROGENITOR CELLS; PLATELETS IN-VITRO
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Creation Date: 1998-03-01 12:00:00
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