骨髓纤维化
鲁索利替尼
骨硬化
骨髓增生性肿瘤
造血
骨髓增生性疾病
JAK2 V617F
癌症研究
细胞因子
白细胞介素3
髓外造血
免疫学
医学
生物
作者
Shivam Rai,Elodie Grockowiak,Nils Hansen,Damien Luque Paz,Cedric B. Stoll,Hui Hao-Shen,Gabriele Mild-Schneider,Stefan Dirnhofer,Christopher J. Farady,Simón Méndez-Ferrer,Radek C. Skoda
标识
DOI:10.1038/s41467-022-32927-4
摘要
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.
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