The Mpl ligand and platelet homeostasis.
The classification of Mpl as a cytokine receptor present on cells of the platelet lineage has led to the identification and cloning of its ligand. This has resulted in a rapid accumulation of data advancing the understanding of the processes of megakaryopoiesis and thrombopoiesis and the regulation of endogenous Mpl ligand (thrombopoietin, eTPO). Highlights of in vitro human and non-human primate data will be discussed, as well as preclinical (in vivo) non-human primate studies. Two recombinant forms of Mpl ligands (rTPO) are currently being tested in clinical trials and early results will be reviewed. The preclinical and clinical studies will be summarized with consideration of the observations which provide insights into the biology of the response to exogenous rTPO. Understanding the biology of platelet production and the condition of target cells in treatment populations will facilitate the appropriate use of this potential therapeutic agent.
Nichol
J L
JL
Department of Pharmacology, Amgen Inc., Thousand Oaks, California, USA.
D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D002986:Clinical Trials as Topic; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D008533:Megakaryocytes / Q000502:physiology*; D009369:Neoplasms / Q000276:immunology / Q000628:therapy; D011323:Primates; D011994:Recombinant Proteins / Q000627:therapeutic use; D013926:Thrombopoietin / Q000502:physiology* / Q000627:therapeutic use*
D011994:Recombinant Proteins; D013926:Thrombopoietin