Interleukin-1 Contributes to Clonal Expansion and Progression of Bone Marrow Fibrosis in JAK2V617F-induced Myeloproliferative Neoplasm

Overview

Journal Nat Commun

Specialty Biology

Date 2022 Sep 13

PMID 36100596

Authors

Mohammed Ferdous-Ur Rahman

Yue Yang

Bao T Le

Avik Dutta

Julia Posyniak

Patrick Faughnan

Mohammad A Sayem

Nadine S Aguilera

Golam Mohi

Affiliations

Soon will be listed here.

Abstract

Chronic inflammation is frequently associated with myeloproliferative neoplasms (MPN), but the role of inflammation in the pathogenesis of MPN remains unclear. Expression of the proinflammatory cytokine interleukin-1 (IL-1) is elevated in patients with MPN as well as in Jak2V617F knock-in mice. Here, we show that genetic deletion of IL-1 receptor 1 (IL-1R1) normalizes peripheral blood counts, reduces splenomegaly and ameliorates bone marrow fibrosis in homozygous Jak2V617F mouse model of myelofibrosis. Deletion of IL-1R1 also significantly reduces Jak2V617F mutant hematopoietic stem/progenitor cells. Exogenous administration of IL-1β enhances myeloid cell expansion and accelerates the development of bone marrow fibrosis in heterozygous Jak2V617F mice. Furthermore, treatment with anti-IL-1R1 antibodies significantly reduces leukocytosis and splenomegaly, and ameliorates bone marrow fibrosis in homozygous Jak2V617F mice. Collectively, these results suggest that IL-1 signaling plays a pathogenic role in MPN disease progression, and targeting of IL-1R1 could be a useful strategy for the treatment of myelofibrosis.

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