
Myeloproliferative leukemia protein activation directly induces fibrocyte differentiation to cause myelofibrosis
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ABSTRACT Myelofibrosis (MF) may be caused by various pathogenic mechanisms such as elevation in circulating cytokine levels, cellular interactions and genetic mutations. However, the
underlying mechanism of MF still remains unknown. Recent studies have revealed that fibrocytes, the spindle-shaped fibroblast-like hematopoietic cells, and the thrombopoietin
(TPO)/myeloproliferative leukemia protein (MPL; TPO receptor) signaling pathway play a certain role in the development of MF. In the present study, we aimed to investigate the relationship
between fibrocytes and MPL activation. We showed that TPO or a TPO receptor agonist directly induces fibrocyte differentiation using murine fibrocyte cell lines and a murine MF model.
Conversely, elimination of macrophages expressing MPL by clodronate liposomes reversed the MF phenotype of the murine model, suggesting that fibrocyte differentiation induced by MPL
activation contributes to the progression of MF. Furthermore, we revealed that SLAMF7high MPLhigh monocytes in human peripheral blood mononuclear cells were possible fibrocyte precursors and
that these cells increased in number in MF patients not treated with ruxolitinib. Our findings confirmed a link between fibrocytes and the TPO/MPL signaling pathway, which could result in a
greater understanding of the pathogenesis of MF and lead to the development of novel therapeutic interventions. Access through your institution Buy or subscribe This is a preview of
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CLONAL EXPANSION AND PROGRESSION OF BONE MARROW FIBROSIS IN JAK2V617F-INDUCED MYELOPROLIFERATIVE NEOPLASM Article Open access 13 September 2022 INHIBITION OF PROINFLAMMATORY SIGNALING
IMPAIRS FIBROSIS OF BONE MARROW MESENCHYMAL STROMAL CELLS IN MYELOPROLIFERATIVE NEOPLASMS Article Open access 14 March 2022 INHIBITION OF ERK1/2 SIGNALING PREVENTS BONE MARROW FIBROSIS BY
REDUCING OSTEOPONTIN PLASMA LEVELS IN A MYELOFIBROSIS MOUSE MODEL Article Open access 16 March 2023 CHANGE HISTORY * _ 19 SEPTEMBER 2018 Owing to the insufficient specificity of the
anti-myeloproliferative leukemia protein (MPL) antibody in the original version of this Article, Figure 6 and parts of Figures 2a, 4e, and 5a do not represent the correct information. The
corrected version of Figure 6 is shown below and those of Figures 2a, 4e, and 5a are shown in the supplemental information. _ REFERENCES * Tefferi A, Lasho TL, Finke CM, Knudson RA,
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_Br J Haematol_ 1997; 99: 281–284. Article CAS PubMed Google Scholar Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Division of Hematology, Department of Internal
Medicine, National Defense Medical College, Tokorozawa, Japan T Maekawa, Y Osawa, T Izumi, S Nagao, K Takano, Y Okada, N Tachi, M Teramoto, T Kawamura, T Horiuchi, R Saga, S Kato, T
Yamamura, J Watanabe, A Kobayashi, S Kobayashi, K Sato & F Kimura * Suzu Project Laboratory, Center for AIDS Research, Kumamoto University, Kumamoto, Japan M Hashimoto & S Suzu
Authors * T Maekawa View author publications You can also search for this author inPubMed Google Scholar * Y Osawa View author publications You can also search for this author inPubMed
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also search for this author inPubMed Google Scholar * S Suzu View author publications You can also search for this author inPubMed Google Scholar * F Kimura View author publications You can
also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to T Maekawa. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no conflict of interest.
RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Maekawa, T., Osawa, Y., Izumi, T. _et al._ Myeloproliferative leukemia protein activation directly
induces fibrocyte differentiation to cause myelofibrosis. _Leukemia_ 31, 2709–2716 (2017). https://doi.org/10.1038/leu.2017.112 Download citation * Received: 18 November 2016 * Revised: 22
March 2017 * Accepted: 28 March 2017 * Published: 03 April 2017 * Issue Date: December 2017 * DOI: https://doi.org/10.1038/leu.2017.112 SHARE THIS ARTICLE Anyone you share the following link
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