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dc.contributor.authorBennett, Cavan
dc.contributor.authorLawrence, Moyra
dc.contributor.authorGuerrero, Jose A
dc.contributor.authorStritt, Simon
dc.contributor.authorWaller, Amie
dc.contributor.authorYan, Yahui
dc.contributor.authorMifsud, Richard W
dc.contributor.authorBallester-Beltrán, Jose
dc.contributor.authorBaig, Ayesha
dc.contributor.authorMueller, Annett
dc.contributor.authorMayer, Louisa
dc.contributor.authorWarland, James
dc.contributor.authorPenkett, Christopher J
dc.contributor.authorAkbari, Parsa
dc.contributor.authorMoreau, Thomas
dc.contributor.authorEvans, Amanda
dc.contributor.authorMookerjee, Souradip
dc.contributor.authorHoffman, Gary J
dc.contributor.authorSaeb-Parsy, Kourosh
dc.contributor.authorAdams, David J
dc.contributor.authorCouzens, Amber L
dc.contributor.authorBender, Markus
dc.contributor.authorErber, Wendy N
dc.contributor.authorNieswandt, Bernhard
dc.contributor.authorRead, Randy
dc.contributor.authorGhevaert, Cedric
dc.date.accessioned2021-11-25T17:29:34Z
dc.date.available2021-11-25T17:29:34Z
dc.date.issued2022-04-07
dc.identifier.issn0006-4971
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/331195
dc.description.abstractThe process of platelet production has so far been understood to be a 2-stage process: megakaryocyte maturation from hematopoietic stem cells followed by proplatelet formation, with each phase regulating the peripheral blood platelet count. Proplatelet formation releases into the bloodstream beads-on-a-string preplatelets, which undergo fission into mature platelets. For the first time, we show that preplatelet maturation is a third, tightly regulated, critical process akin to cytokinesis that regulates platelet count. We show that deficiency in cytokine receptor-like factor 3 (CRLF3) in mice leads to an isolated and sustained 25% to 48% reduction in the platelet count without any effect on other blood cell lineages. We show that Crlf3-/- preplatelets have increased microtubule stability, possibly because of increased microtubule glutamylation via the interaction of CRLF3 with key members of the Hippo pathway. Using a mouse model of JAK2 V617F essential thrombocythemia, we show that a lack of CRLF3 leads to long-term lineage-specific normalization of the platelet count. We thereby postulate that targeting CRLF3 has therapeutic potential for treatment of thrombocythemia.
dc.publisherAmerican Society of Hematology
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectStemCellInsitute
dc.titleCRLF3 plays a key role in the final stage of platelet genesis and is a potential therapeutic target for thrombocythemia.
dc.typeArticle
prism.publicationNameBlood
dc.identifier.doi10.17863/CAM.78642
dcterms.dateAccepted2021-11-23
rioxxterms.versionofrecord10.1182/blood.2021013113
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
dc.contributor.orcidBennett, Cavan [0000-0002-9796-9381]
dc.contributor.orcidLawrence, Moyra [0000-0001-9386-5633]
dc.contributor.orcidWaller, Amie [0000-0002-9726-5560]
dc.contributor.orcidYan, Yahui [0000-0001-6934-9874]
dc.contributor.orcidBallester-Beltrán, Jose [0000-0002-3287-2925]
dc.contributor.orcidMayer, Louisa [0000-0003-4905-0669]
dc.contributor.orcidWarland, James [0000-0003-1060-1865]
dc.contributor.orcidPenkett, Christopher J [0000-0003-4006-7261]
dc.contributor.orcidAkbari, Parsa [0000-0001-9210-4760]
dc.contributor.orcidMoreau, Thomas [0000-0003-1090-6685]
dc.contributor.orcidMookerjee, Souradip [0000-0003-4904-1324]
dc.contributor.orcidSaeb-Parsy, Kourosh [0000-0002-0633-3696]
dc.contributor.orcidAdams, David J [0000-0001-9490-0306]
dc.contributor.orcidCouzens, Amber L [0000-0003-0057-6686]
dc.contributor.orcidBender, Markus [0000-0002-2381-116X]
dc.contributor.orcidErber, Wendy N [0000-0002-1028-9376]
dc.contributor.orcidNieswandt, Bernhard [0000-0003-1454-7413]
dc.contributor.orcidRead, Randy [0000-0001-8273-0047]
dc.contributor.orcidGhevaert, Cedric [0000-0002-9251-0934]
dc.identifier.eissn1528-0020
rioxxterms.typeJournal Article/Review
pubs.funder-project-idWellcome Trust (203151/Z/16/Z)
pubs.funder-project-idBritish Heart Foundation (None)
pubs.funder-project-idMedical Research Council (MR/R015724/1)
pubs.funder-project-idMedical Research Council (MR/V005413/1)
pubs.funder-project-idMedical Research Council (MC_PC_17230)
cam.issuedOnline2022-01-20


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International