Neoplastic fibrocytes play an essential role in bone marrow fibrosis in Jak2V617F-induced primary myelofibrosis mice.
Journal
Leukemia
ISSN: 1476-5551
Titre abrégé: Leukemia
Pays: England
ID NLM: 8704895
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
30
01
2020
accepted:
18
05
2020
revised:
07
05
2020
pubmed:
31
5
2020
medline:
26
2
2021
entrez:
31
5
2020
Statut:
ppublish
Résumé
Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) characterized by clonal myeloproliferation, progressive bone marrow (BM) fibrosis, splenomegaly, and anemia. BM fibrosis was previously thought to be a reactive phenomenon induced by mesenchymal stromal cells that are stimulated by the overproduction of cytokines such as transforming growth factor (TGF)-β1. However, the involvement of neoplastic fibrocytes in BM fibrosis was recently reported. In this study, we showed that the vast majority of collagen- and fibronectin-producing cells in the BM and spleens of Jak2V617F-induced myelofibrosis (MF) mice were fibrocytes derived from neoplastic hematopoietic cells. Neoplastic monocyte depletion eliminated collagen- and fibronectin-producing fibrocytes in BM and spleen, and ameliorated most characteristic MF features in Jak2V617F transgenic mice, including BM fibrosis, anemia, and splenomegaly, while had little effect on the elevated numbers of megakaryocytes and stem cells in BM, and leukothrombocytosis in peripheral blood. TGF-β1, which was produced by hematopoietic cells including fibrocytes, promoted the differentiation of neoplastic monocytes to fibrocytes, and elevated plasma TGF-β1 levels were normalized by monocyte depletion. Collectively, our data suggest that neoplastic fibrocytes are the major contributor to BM fibrosis in PMF, and TGF-β1 is required for their differentiation.
Identifiants
pubmed: 32472085
doi: 10.1038/s41375-020-0880-3
pii: 10.1038/s41375-020-0880-3
pmc: PMC7862060
doi:
Substances chimiques
Tgfb1 protein, mouse
0
Transforming Growth Factor beta1
0
Jak2 protein, mouse
EC 2.7.10.2
Janus Kinase 2
EC 2.7.10.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
454-467Subventions
Organisme : MEXT | Japan Society for the Promotion of Science (JSPS)
ID : 19K17404
Organisme : MEXT | Japan Society for the Promotion of Science (JSPS)
ID : 19K08819
Organisme : MEXT | Japan Society for the Promotion of Science (JSPS)
ID : 19K17834
Organisme : MEXT | Japan Society for the Promotion of Science (JSPS)
ID : 17H04210
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