The thrombopoietin receptor: revisiting the master regulator of platelet production

DC FieldValueLanguage
dc.contributor.authorHitchcock, Ian S.
dc.contributor.authorHafer, Maximillian
dc.contributor.authorSangkhae, Veena
dc.contributor.authorTucker, Julie A.
dc.date.accessioned2021-12-23T16:18:46Z-
dc.date.available2021-12-23T16:18:46Z-
dc.date.issued2021
dc.identifier.issn09537104
dc.identifier.urihttps://osnascholar.ub.uni-osnabrueck.de/handle/unios/12836-
dc.description.abstractThrombopoietin (TPO) and its receptor, MPL, are the primary regulators of platelet production and critical for hematopoietic stem cell (HSC) maintenance. Since TPO was first cloned in 1994, the physiological and pathological roles of TPO and MPL have been well characterized, culminating in the first MPL agonists being approved for the treatment of chronic immune thrombocytopenia in 2008. Dysregulation of the TPO-MPL signaling axis contributes to the pathogenesis of hematological disorders: decreased expression or function results in severe thrombocytopenia progressing to bone marrow failure, while hyperactivation of MPL signaling, either by mutations in the receptor or associated Janus kinase 2 (JAK2), results in pathological myeloproliferation. Despite its importance, it was only recently that the long-running debate over the mechanism by which TPO binding activates MPL has been resolved. This review will cover key aspects of TPO and MPL structure and function and their importance in receptor activation, discuss how these are altered in hematological disorders and consider how a greater understanding could lead to the development of better-targeted and more efficacious therapies.
dc.description.sponsorshipCancer Research UKCancer Research UK [A24593]; German Research Foundation (Deutsche Forschungsgemeinschaft)German Research Foundation (DFG) [PI 405/15]; National Institutes of Health National Institute of Diabetes and Digestive and Kidney DiseasesUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) [K01DK127004]; This work was supported by Cancer Research UK [A24593]; German Research Foundation (Deutsche Forschungsgemeinschaft) [PI 405/15]; National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [K01DK127004].
dc.language.isoen
dc.publisherTAYLOR & FRANCIS INC
dc.relation.ispartofPLATELETS
dc.subjectACTIVATION
dc.subjectC-MPL MUTATIONS
dc.subjectCell Biology
dc.subjectGENE
dc.subjectGLYCAN DOMAIN
dc.subjectHematology
dc.subjectHEPATIC THROMBOPOIETIN
dc.subjectHEREDITARY THROMBOCYTHEMIA
dc.subjectIDENTIFICATION
dc.subjectMEGAKARYOCYTE GROWTH
dc.subjectmegakaryocytes
dc.subjectplatelets
dc.subjectsignaling
dc.subjectSPLICE DONOR MUTATION
dc.subjectTHROMBOCYTOPENIA
dc.subjectThrombopoietin
dc.subjectthrombopoietin receptor
dc.titleThe thrombopoietin receptor: revisiting the master regulator of platelet production
dc.typejournal article
dc.identifier.doi10.1080/09537104.2021.1925102
dc.identifier.isiISI:000658644300001
dc.description.volume32
dc.description.issue6
dc.description.startpage770
dc.description.endpage778
dc.contributor.orcid0000-0002-6119-676X
dc.contributor.researcheridAAT-1513-2021
dc.identifier.eissn13691635
dc.publisher.place530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
dcterms.isPartOf.abbreviationPlatelets
dcterms.oaStatusGreen Published, hybrid, Green Accepted
Show simple item record

Google ScholarTM

Check

Altmetric