Novel mechanisms of platelet clearance and thrombopoietin regulation. Curr Opin Hematol 2015 Sep;22(5):445-51
Date
07/15/2015Pubmed ID
26154508Pubmed Central ID
PMC5326579DOI
10.1097/MOH.0000000000000170Scopus ID
2-s2.0-84942764882 (requires institutional sign-in at Scopus site) 53 CitationsAbstract
PURPOSE OF REVIEW: The human body produces and removes 10 platelets daily to maintain a normal steady-state platelet count. Platelet production must be tightly regulated to avoid spontaneous bleeding or arterial occlusion and organ damage. Multifaceted and complex mechanisms control platelet removal and production in physiological and pathological conditions. This review will focus on different mechanisms of platelet clearance, with focus on the biological significance of platelet glycans.
RECENT FINDINGS: The Ashwell-Morrell receptor (AMR) recognizes senescent, desialylated platelets under steady state conditions. Desialylated platelets and the AMR are the physiological ligand-receptor pair regulating hepatic thrombopoietin (TPO) mRNA production, resolving the longstanding mystery of steady state TPO regulation. The AMR-mediated removal of desialylated platelets regulates TPO synthesis in the liver by recruiting JAK2 and STAT3 to increase thrombopoiesis.
SUMMARY: Inhibition of TPO production downstream of the hepatic AMR-JAK2 signaling cascade could additionally contribute to the thrombocytopenia associated with JAK1/2 treatment, which is clinically used in myeloproliferative neoplasms.
Author List
Grozovsky R, Giannini S, Falet H, Hoffmeister KMAuthors
Herve Falet PhD Associate Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinKarin Hoffmeister MD Professor in the Biochemistry department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Blood PlateletsCellular Senescence
Humans
Janus Kinase 2
Liver
Platelet Count
RNA, Messenger
STAT3 Transcription Factor
Signal Transduction
Thrombocytopenia
Thrombopoiesis
Thrombopoietin
