論文

国際誌
2021年2月

Neoplastic fibrocytes play an essential role in bone marrow fibrosis in Jak2V617F-induced primary myelofibrosis mice.

Leukemia
  • Yoshinori Ozono
  • Kotaro Shide
  • Takuro Kameda
  • Ayako Kamiunten
  • Yuki Tahira
  • Masaaki Sekine
  • Keiichi Akizuki
  • Kenichi Nakamura
  • Hisayoshi Iwakiri
  • Mitsue Sueta
  • Tomonori Hidaka
  • Yoko Kubuki
  • Shojiro Yamamoto
  • Satoru Hasuike
  • Akira Sawaguchi
  • Kenji Nagata
  • Kazuya Shimoda
  • 全て表示

35
2
開始ページ
454
終了ページ
467
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/s41375-020-0880-3

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.

リンク情報
DOI
https://doi.org/10.1038/s41375-020-0880-3
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/32472085
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862060
ID情報
  • DOI : 10.1038/s41375-020-0880-3
  • PubMed ID : 32472085
  • PubMed Central 記事ID : PMC7862060

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