Inhibition of interleukin-1β reduces myelofibrosis and osteosclerosis in mice with JAK2-V617F driven myeloproliferative neoplasm.

Autor: Rai S; Department of Biomedicine, Experimental Hematology, University Hospital Basel, University of Basel, 4031, Basel, Switzerland., Grockowiak E; Wellcome-MRC Cambridge Stem Cell Institute, Cambridge, CB2 0AW, UK.; Department of Hematology, University of Cambridge, Cambridge, CB2 0AW, UK.; National Health Service Blood and Transplant, Cambridge Biomedical Campus, Cambridge, CB2 0AW, UK., Hansen N; Department of Biomedicine, Experimental Hematology, University Hospital Basel, University of Basel, 4031, Basel, Switzerland., Luque Paz D; Department of Biomedicine, Experimental Hematology, University Hospital Basel, University of Basel, 4031, Basel, Switzerland., Stoll CB; Department of Biomedicine, Experimental Hematology, University Hospital Basel, University of Basel, 4031, Basel, Switzerland., Hao-Shen H; Department of Biomedicine, Experimental Hematology, University Hospital Basel, University of Basel, 4031, Basel, Switzerland., Mild-Schneider G; Department of Biomedicine, Experimental Hematology, University Hospital Basel, University of Basel, 4031, Basel, Switzerland., Dirnhofer S; Department of Pathology, University Hospital Basel, 4031, Basel, Switzerland., Farady CJ; Novartis Institutes for BioMedical Research Forum 1, Basel, Switzerland., Méndez-Ferrer S; Wellcome-MRC Cambridge Stem Cell Institute, Cambridge, CB2 0AW, UK.; Department of Hematology, University of Cambridge, Cambridge, CB2 0AW, UK.; National Health Service Blood and Transplant, Cambridge Biomedical Campus, Cambridge, CB2 0AW, UK., Skoda RC; Department of Biomedicine, Experimental Hematology, University Hospital Basel, University of Basel, 4031, Basel, Switzerland. radek.skoda@unibas.ch.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Sep 13; Vol. 13 (1), pp. 5346. Date of Electronic Publication: 2022 Sep 13.
DOI: 10.1038/s41467-022-32927-4
Abstrakt: Interleukin-1β (IL-1β) is a master regulator of inflammation. Increased activity of IL-1β has been implicated in various pathological conditions including myeloproliferative neoplasms (MPNs). Here we show that IL-1β serum levels and expression of IL-1 receptors on hematopoietic progenitors and stem cells correlate with JAK2-V617F mutant allele fraction in peripheral blood of patients with MPN. We show that the source of IL-1β overproduction in a mouse model of MPN are JAK2-V617F expressing hematopoietic cells. Knockout of IL-1β in hematopoietic cells of JAK2-V617F mice reduces inflammatory cytokines, prevents damage to nestin-positive niche cells and reduces megakaryopoiesis, resulting in decrease of myelofibrosis and osteosclerosis. Inhibition of IL-1β in JAK2-V617F mutant mice by anti-IL-1β antibody also reduces myelofibrosis and osteosclerosis and shows additive effects with ruxolitinib. These results suggest that inhibition of IL-1β with anti-IL-1β antibody alone or in combination with ruxolitinib could have beneficial effects on the clinical course in patients with myelofibrosis.
(© 2022. The Author(s).)
Databáze: MEDLINE
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