Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/16636
Title
Endogenous IL-1 receptor antagonist restricts healthy and malignant myeloproliferation.
Author(s)
Villatoro, Alicia | Cuminetti, Vincent | Bernal, Aurora CNIC | Torroja, Carlos CNIC | Cossío, Itziar | Benguría, Alberto | Ferré, Marc | Konieczny, Joanna | Vázquez, Enrique | Rubio, Andrea | Utnes, Peter | Tello, Almudena | You, Xiaona | Fenton, Christopher G | Paulssen, Ruth H | Zhang, Jing | Sanchez-Cabo, Fatima CNIC | Dopazo, Ana CNIC | Vik, Anders | Anderssen, Endre | Hidalgo, Andrés | Arranz, Lorena CNIC
Date issued
2023-01-03
Citation
Nat Commun. 2023 Jan 3;14(1):12.
Language
Inglés
Document type
journal article
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.
MESH
Receptors, Interleukin-1 | Leukemia, Myeloid, Acute | Humans | Bone Marrow | Cell Proliferation | Antigens, CD34
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