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Description of a knock-in mouse model of JAK2V617F MPN emerging from a minority of mutated hematopoietic stem cells

dc.rights.licenseauthentificationen_US
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorMANSIER, Olivier
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorKILANI, Badr
dc.contributor.authorGUITART, Amélie V.
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorGUY, Alexandre
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorGOURDOU-LATYSZENOK, Virginie
dc.contributor.authorMARTY, Caroline
dc.contributor.authorPARRENS, Marie
dc.contributor.authorPLO, Isabelle
dc.contributor.authorVAINCHENKER, William
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorJAMES, Chloé
dc.date.accessioned2020-11-10T11:36:30Z
dc.date.available2020-11-10T11:36:30Z
dc.date.issued2019-12
dc.identifier.issn0006-4971, 1528-0020en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/12201
dc.description.abstractEnThe major weakness of most knock-in JAK2V617F mouse models is the presence of the JAK2 mutation in all rather than in a few hematopoietic stem cells (HSC), such as in human "early-stage" myeloproliferative neoplasms (MPN). Understanding the mechanisms of disease initiation is critical as underscored by the incidence of clonal hematopoiesis of indeterminate potential associated with JAK2V617F. Currently, such studies require competitive transplantation. Here, we report a mouse model obtained by crossing JAK2V617F/WT knock-in mice with PF4iCre transgenic mice. As expected, PF4iCre;JAK2V617F/WT mice developed an early thrombocytosis resulting from the expression of JAK2V617F in the megakaryocytes. However, these mice then developed a polycythemia vera-like phenotype at 10 weeks of age. Using mT/mG reporter mice, we demonstrated that Cre recombination was present in all hematopoietic compartments, including in a low number of HSC. The frequency of mutated cells increased along hematopoietic differentiation mimicking the clonal expansion observed in essential thrombocythemia and polycythemia vera patients. This model thus mimics the HSC compartment observed in early-stage MPN, with a small number of JAK2V617F HSC competing with a majority of JAK2WT HSC. PF4iCre;JAK2V617F/WT mice are a promising tool to investigate the mechanisms that regulate clonal dominance and progression to myelofibrosis.
dc.language.isoENen_US
dc.subjectArticle RECHERCHE
dc.title.enDescription of a knock-in mouse model of JAK2V617F MPN emerging from a minority of mutated hematopoietic stem cells
dc.typeArticle de revueen_US
dc.identifier.doi10.1182/blood.2019001163en_US
dc.subject.halSciences du Vivant [q-bio]/Médecine humaine et pathologieen_US
bordeaux.journalBlooden_US
bordeaux.page2383–2387en_US
bordeaux.volume134en_US
bordeaux.hal.laboratoriesBiologie des maladies cardiovasculaires - U1034en_US
bordeaux.issue26en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.identifierhal-03194452
hal.version1
hal.date.transferred2021-04-09T13:18:55Z
hal.exporttrue
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