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Gray platelet syndrome: proinflammatory megakaryocytes and α-granule loss cause myelofibrosis and confer metastasis resistance in mice

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dc.contributor.authorGuerrero López, José Antonio
dc.contributor.authorBennett, Cavan
dc.contributor.authorWeyden, Louise van der
dc.contributor.authorMcKinney, Harriet
dc.contributor.authorChin, Melody
dc.contributor.authorNurden, Paquita
dc.contributor.authorMcIntyre, Zoe
dc.contributor.authorCambridge, Emma L.
dc.contributor.authorEstabel, Jeanne
dc.contributor.authorWardle Jones, Hannah
dc.contributor.authorSpeak, Anneliese O.
dc.contributor.authorErber, Wendy N.
dc.contributor.authorRendon, Augusto
dc.contributor.authorOuwehand, Willem H.
dc.contributor.authorGhevaer, Cedric
dc.contributor.departmentMedicina
dc.date.accessioned2026-02-23T12:26:34Z
dc.date.available2026-02-23T12:26:34Z
dc.date.copyright© 2014 by The American Society of Hematology
dc.date.issued2014-12-04
dc.description.abstractNBEAL2 encodes a multidomain scaffolding protein with a putative role in granule ontogeny in human platelets. Mutations in NBEAL2 underlie gray platelet syndrome (GPS), a rare inherited bleeding disorder characterized by a lack of α-granules within blood platelets and progressive bone marrow fibrosis. We present here a novel Nbeal2−/− murine model of GPS and demonstrate that the lack of α-granules is due to their loss from platelets/mature megakaryocytes (MKs), and not by initial impaired formation. We show that the lack of Nbeal2 confers a proinflammatory phenotype to the bone marrow MKs, which in combination with the loss of proteins from α-granules drives the development of bone marrow fibrosis. In addition, we demonstrate that α-granule deficiency impairs platelet function beyond their purely hemostatic role and that Nbeal2 deficiency has a protective effect against cancer metastasis.
dc.formatapplication/pdf
dc.format.extent13
dc.identifier.citationBlood, Volume 124, Issue 24, 4 December 2014, Pages 3624-3635
dc.identifier.doihttps://doi.org/10.1182/blood-2014-04-566760
dc.identifier.eissn1528-0020
dc.identifier.issn0006-4971
dc.identifier.urihttp://hdl.handle.net/10201/210721
dc.languageeng
dc.publisherAmerican Society of Hematology (ASH Publications)
dc.relationThis work was funded by the British Heart Foundation (grant FS09/039) (C.G.) and (grant RG/09/12/28096) (W.H.O. and A.R.), the National Health Service: Blood and Transplant grant (C.B. and H.M.); and the Wellcome Trust (grant WT098051) (Z.M., E.L.C., J.E., H.W.J., and A.O.S.).
dc.relation.publisherversionhttps://www.sciencedirect.com/science/article/pii/S0006497120396154
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subject.odsObjetivo 3: Salud
dc.titleGray platelet syndrome: proinflammatory megakaryocytes and α-granule loss cause myelofibrosis and confer metastasis resistance in mice
dc.typeinfo:eu-repo/semantics/article
dc.type.versioninfo:eu-repo/semantics/publishedVersion
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relation.isAuthorOfPublication099fb9a8-9bae-43fb-be04-b8ea37502882
relation.isAuthorOfPublication.latestForDiscovery099fb9a8-9bae-43fb-be04-b8ea37502882
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