Mechanism of action and clinical trials of Mpl ligand.
Mpl ligand is the hematopoietic growth factor responsible for regulating the production of platelets. Since its discovery just 3 years ago, it has provided both unique insights into megakaryocytopoiesis and the means to stimulate platelet production in numerous clinical situations. In animals deficient in Mpl ligand, the number of megakaryocytes and platelets decreases by more than 80%. In addition to having an effect on the megakaryocyte lineage, Mpl ligand supports the growth of stem cells, multipotential cells, and erythroid precursors. The endogenous Mpl ligand, thrombopoietin, is produced in the liver and kidneys, and circulating levels appear to be regulated primarily by the mass of platelets and megakaryocytes, which bind and catabolize Mpl ligand. The clinical utility of recombinant Mpl ligands is currently under intense investigation. Early results have demonstrated a marked stimulation of megakaryocyte and platelet production with no apparent adverse effects. In patients with cancer who are treated with chemotherapy, the duration of thrombocytopenia was shorter in patients treated with Mpl ligand than in those receiving placebo. The eventual role of Mpl ligand in clinical practice will be determined by the results of many ongoing clinical studies.
Sheridan
W P
WP
Amgen, Inc., Thousand Oaks, CA 91320, USA.
Kuter
D J
DJ
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017321:Clinical Trials, Phase I as Topic; D015870:Gene Expression; D006410:Hematopoiesis; D006801:Humans; D008533:Megakaryocytes / Q000166:cytology*; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy*; D011092:Polyethylene Glycols; D013926:Thrombopoietin / Q000008:administration & dosage / Q000235:genetics / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D011092:Polyethylene Glycols; D013926:Thrombopoietin