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dc.contributor.authorVillatoro, Alicia
dc.contributor.authorCuminetti, Vincent
dc.contributor.authorBernal, Aurora
dc.contributor.authorTorroja, Carlos
dc.contributor.authorCossío, Itziar
dc.contributor.authorBenguría, Alberto
dc.contributor.authorFerré, Marc
dc.contributor.authorKonieczny, Joanna
dc.contributor.authorVázquez, Enrique
dc.contributor.authorRubio, Andrea
dc.contributor.authorUtnes, Peter Andree
dc.contributor.authorYou, Xiaona
dc.contributor.authorFenton, Christopher Graham
dc.contributor.authorPaulssen, Ruth H
dc.contributor.authorZhang, Jing
dc.contributor.authorSánchez-Cabo, Fatima
dc.contributor.authorDopazo, Ana
dc.contributor.authorVik, Anders
dc.contributor.authorAnderssen, Endre
dc.contributor.authorHidalgo, Andres
dc.contributor.authorArranz, Lorena
dc.date.accessioned2023-08-22T10:32:50Z
dc.date.available2023-08-22T10:32:50Z
dc.date.issued2023-01-03
dc.description.abstractHere we explored the role of interleukin-1β (IL-1β) repressor cytokine, IL-1 receptor antagonist (IL-1rn), in both healthy and abnormal hematopoiesis. Low IL-1RN is frequent in acute myeloid leukemia (AML) patients and represents a prognostic marker of reduced survival. Treatments with IL-1RN and the IL-1β monoclonal antibody canakinumab reduce the expansion of leukemic cells, including CD34+ progenitors, in AML xenografts. In vivo deletion of IL-1rn induces hematopoietic stem cell (HSC) differentiation into the myeloid lineage and hampers B cell development via transcriptional activation of myeloid differentiation pathways dependent on NFκB. Low IL-1rn is present in an experimental model of pre-leukemic myelopoiesis, and IL-1rn deletion promotes myeloproliferation, which relies on the bone marrow hematopoietic and stromal compartments. Conversely, IL-1rn protects against pre-leukemic myelopoiesis. Our data reveal that HSC differentiation is controlled by balanced IL-1β/IL-1rn levels under steady-state, and that loss of repression of IL-1β signaling may underlie pre-leukemic lesion and AML progression.en_US
dc.identifier.citationVillatoro AE, Cuminetti V, Bernal A, Torroja, Cossío, Benguría, Ferré, Konieczny J, Vázquez, Rubio, Utnes PA, You, Fenton CG, Paulssen RH, Zhang J, Sánchez-Cabo, Dopazo, Vik A, Anderssen E, Hidalgo, Arranz L. Endogenous IL-1 receptor antagonist restricts healthy and malignant myeloproliferation. Nature Communications. 2023;14en_US
dc.identifier.cristinIDFRIDAID 2102650
dc.identifier.doi10.1038/s41467-022-35700-9
dc.identifier.issn2041-1723
dc.identifier.urihttps://hdl.handle.net/10037/30158
dc.language.isoengen_US
dc.publisherSpringer Natureen_US
dc.relation.journalNature Communications
dc.relation.projectIDKreftforeningen: 6765150en_US
dc.relation.projectIDNorges forskningsråd: 250901en_US
dc.relation.projectIDNorges forskningsråd: 247596en_US
dc.relation.projectIDUiT Norges arktiske universitet: Strategisk-HN06-14en_US
dc.relation.projectIDRegionalt helseforetak: HNF1338-17en_US
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2023 The Author(s)en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0en_US
dc.rightsAttribution 4.0 International (CC BY 4.0)en_US
dc.titleEndogenous IL-1 receptor antagonist restricts healthy and malignant myeloproliferationen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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Attribution 4.0 International (CC BY 4.0)
Med mindre det står noe annet, er denne innførselens lisens beskrevet som Attribution 4.0 International (CC BY 4.0)