2026-04-17T23:00:33Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/166362024-09-27T07:57:11Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Villatoro, Alicia author Cuminetti, Vincent author Bernal, Aurora author Torroja, Carlos author Cossío, Itziar author Benguría, Alberto author Ferré, Marc author Konieczny, Joanna author Vázquez, Enrique author Rubio, Andrea author Utnes, Peter author Tello, Almudena author You, Xiaona author Fenton, Christopher G author Paulssen, Ruth H author Zhang, Jing author Sanchez-Cabo, Fatima author Dopazo, Ana author Vik, Anders author Anderssen, Endre author Hidalgo, Andrés author Arranz, Lorena author 2023-01-03 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. Nat Commun. 2023 Jan 3;14(1):12. http://hdl.handle.net/20.500.12105/16636 36596811 10.1038/s41467-022-35700-9 2041-1723 Nature communications Endogenous IL-1 receptor antagonist restricts healthy and malignant myeloproliferation.