dc.contributor.author | Villatoro, Alicia | |
dc.contributor.author | Cuminetti, Vincent | |
dc.contributor.author | Bernal, Aurora | |
dc.contributor.author | Torroja, Carlos | |
dc.contributor.author | Cossío, Itziar | |
dc.contributor.author | Benguría, Alberto | |
dc.contributor.author | Ferré, Marc | |
dc.contributor.author | Konieczny, Joanna | |
dc.contributor.author | Vázquez, Enrique | |
dc.contributor.author | Rubio, Andrea | |
dc.contributor.author | Utnes, Peter Andree | |
dc.contributor.author | You, Xiaona | |
dc.contributor.author | Fenton, Christopher Graham | |
dc.contributor.author | Paulssen, Ruth H | |
dc.contributor.author | Zhang, Jing | |
dc.contributor.author | Sánchez-Cabo, Fatima | |
dc.contributor.author | Dopazo, Ana | |
dc.contributor.author | Vik, Anders | |
dc.contributor.author | Anderssen, Endre | |
dc.contributor.author | Hidalgo, Andres | |
dc.contributor.author | Arranz, Lorena | |
dc.date.accessioned | 2023-08-22T10:32:50Z | |
dc.date.available | 2023-08-22T10:32:50Z | |
dc.date.issued | 2023-01-03 | |
dc.description.abstract | Here 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.citation | Villatoro 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;14 | en_US |
dc.identifier.cristinID | FRIDAID 2102650 | |
dc.identifier.doi | 10.1038/s41467-022-35700-9 | |
dc.identifier.issn | 2041-1723 | |
dc.identifier.uri | https://hdl.handle.net/10037/30158 | |
dc.language.iso | eng | en_US |
dc.publisher | Springer Nature | en_US |
dc.relation.journal | Nature Communications | |
dc.relation.projectID | Kreftforeningen: 6765150 | en_US |
dc.relation.projectID | Norges forskningsråd: 250901 | en_US |
dc.relation.projectID | Norges forskningsråd: 247596 | en_US |
dc.relation.projectID | UiT Norges arktiske universitet: Strategisk-HN06-14 | en_US |
dc.relation.projectID | Regionalt helseforetak: HNF1338-17 | en_US |
dc.rights.accessRights | openAccess | en_US |
dc.rights.holder | Copyright 2023 The Author(s) | en_US |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | en_US |
dc.rights | Attribution 4.0 International (CC BY 4.0) | en_US |
dc.title | Endogenous IL-1 receptor antagonist restricts healthy and malignant myeloproliferation | en_US |
dc.type.version | publishedVersion | en_US |
dc.type | Journal article | en_US |
dc.type | Tidsskriftartikkel | en_US |
dc.type | Peer reviewed | en_US |