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Hamostaseologie 1996; 16(02): 107-113
DOI: 10.1055/s-0038-1656646
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Schattauer GmbH

Discovery, in vitro and in vivo Biology of c-mpl Ligand

C. F. Toombs
1   Departments of Pharmacology, California, USA
,
W. P. Sheridan
2   Development, Amgen, Inc. Thousand Oaks, California, USA
› Institutsangaben
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Publikationsdatum:
23. Juli 2018 (online)

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Summary

Since the announcement of the discovery of thrombopoietin in 1994, a tremendous amount of research has determined that recombinant c-mpl ligand (ML) is capable of producing the biological effects of a Meg-CSF and thrombopoietin. Thrombopoietin's effects include the stimulation of primitive hematopoietic stem cells, megakaryocyte progenitor cells, megakaryocyte production and maturation and leading to the formation of platelets both in vitro and in vivo. Animal models of chemotherapy-induced thrombocytopenia have yielded data which fore-shadows a beneficial effect of thrombopoietin in clinical thrombocytopenia. The signaling mechanisms transducing thrombopoietin's actions are currently under research but in progenitor cells most likely involve modulation of the expression of genes regulated by the Jak-STAT signaling pathways, given throm-bopoietin's similarity to erythropoietin. Remnants of the Janus kinase signaling system appear to be active in the platelet and mediate enhanced platelet aggre-gation in response to platelet agonists upon stimulation of the c-mpl receptor with ML. The observation of enhanced platelet aggregation in vitro has not translated to enhanced thrombosis in relevant in vivo animal models. Preliminary clinical reports are returning clear evidence that the lineage-dominant effects of rHuMGDF on megakaryocytopoiesis observed in experimental settings are also holding true in the clinic.

Keywords

rHuMGDF - thrombopoietin - thrombosis - platelet - cyclic flow reduction - aggregation
 

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