Chronic myeloproliferative neoplasms

Myeloproliferative leukemia protein activation directly induces fibrocyte differentiation to cause myelofibrosis

  • A Correction to this article was published on 19 September 2018

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.

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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.

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Correspondence to T Maekawa.

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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

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