Inhibition of interleukin-1β reduces myelofibrosis and osteosclerosis in mice with JAK2-V617F driven myeloproliferative neoplasm
| Autor: | Rai, Shivam, Grockowiak, Elodie, Hansen, Nils, Luque Paz, Damien, Stoll, Cedric B, Hao-Shen, Hui, Mild-Schneider, Gabriele, Dirnhofer, Stefan, Farady, Christopher J, Méndez-Ferrer, Simón, Skoda, Radek C |
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| Přispěvatelé: | Farady, Christopher J [0000-0002-3607-9721], Skoda, Radek C [0000-0002-3626-9496], Apollo - University of Cambridge Repository |
| Rok vydání: | 2022 |
| Předmět: |
Interleukin-1beta
General Physics and Astronomy 38/90 631/67/1990/2331 14 General Biochemistry Genetics and Molecular Biology 38/91 Mice 13/1 13/21 13/100 Neoplasms Nitriles Animals 14/19 692/308/2778 Mice Knockout Multidisciplinary Myeloproliferative Disorders article General Chemistry 64/110 Janus Kinase 2 13/31 Pyrimidines Primary Myelofibrosis 13/51 14/63 38/77 Pyrazoles 64/60 38/39 692/4028/67/1990/2331 Osteosclerosis |
| Popis: | 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 withJAK2-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 areJAK2-V617F expressing hematopoietic cells. Knockout ofIL-1βin hematopoietic cells ofJAK2-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 inJAK2-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. |
| Databáze: | OpenAIRE |
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