Inhibition of interleukin-1ß reduces myelofibrosis and osteosclerosis in mice with JAK2-V617F driven myeloproliferative neoplasm.
Nat Commun
; 13(1): 5346, 2022 09 13.
Article
em En
| MEDLINE
| ID: mdl-36100613
ABSTRACT
Interleukin-1ß (IL-1ß) is a master regulator of inflammation. Increased activity of IL-1ß has been implicated in various pathological conditions including myeloproliferative neoplasms (MPNs). Here we show that IL-1ß 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-1ß overproduction in a mouse model of MPN are JAK2-V617F expressing hematopoietic cells. Knockout of IL-1ß 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-1ß in JAK2-V617F mutant mice by anti-IL-1ß antibody also reduces myelofibrosis and osteosclerosis and shows additive effects with ruxolitinib. These results suggest that inhibition of IL-1ß with anti-IL-1ß antibody alone or in combination with ruxolitinib could have beneficial effects on the clinical course in patients with myelofibrosis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Osteosclerose
/
Janus Quinase 2
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Interleucina-1beta
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Mielofibrose Primária
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Transtornos Mieloproliferativos
/
Neoplasias
Limite:
Animals
Idioma:
En
Revista:
Nat Commun
Assunto da revista:
BIOLOGIA
/
CIENCIA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Suíça