The role of fibrocytes in myelofibrosis and fibrocyte regulation as a novel treatment approach

DOI Web Site PubMed
  • MAEKAWA Takaaki
    Division of Hematology, Department of Internal Medicine, National Defense Medical College
  • KATO Shoichiro
    Division of Hematology, Department of Internal Medicine, National Defense Medical College
  • KIMURA Fumihiko
    Division of Hematology, Department of Internal Medicine, National Defense Medical College

Bibliographic Information

Other Title
  • 骨髄線維症におけるfibrocyte
  • 骨髄線維症におけるfibrocyte : その役割と制御による新規治療へのアプローチ
  • コツズイ センイショウ ニ オケル fibrocyte : ソノ ヤクワリ ト セイギョ ニ ヨル シンキ チリョウ エ ノ アプローチ
  • —その役割と制御による新規治療へのアプローチ—

Search this article

Abstract

<p>Recently, monocyte-derived fibroblast-like cells, called fibrocytes, garnered attention as involved in the novel pathogenesis of various fibrotic diseases. They also play a role in the induction of myelofibrosis (MF). Neoplastic fibrocytes are overrepresented in the bone marrow of patients with primary MF, and the suppression of fibrocyte differentiation by serum amyloid P has been shown to remarkably improve MF. Further, thrombopoietin (TPO) or a TPO receptor agonist directly induces fibrocyte differentiation, and fibrocyte elimination reversed the MF phenotype in a murine model. Human fibrocytes highly express signaling lymphocytic activation molecule-F7 (SLAMF7) compared with macrophages. Myeloproliferative neoplasm (MPN) patients harboring JAK2V617F with MF had a significantly elevated SLAMF7high monocyte percentage, which correlated positively with the JAK2V617F allele burden. Furthermore, the JAK2V617F allele burden and the tendency to differentiate into fibrocytes of SLAMF7high monocytes was significantly higher than that of JAK2V617Flow monocytes and could be a potential target of elotuzumab (Elo), an anti-SLAMF7 antibody used to treat multiple myeloma. Elo independently inhibited the differentiation of fibrocytes derived not only from healthy controls but also from MF patients in vitro. Elo also ameliorated MF and splenomegaly induced by romiplostim administration in humanized NOG mice. Thus, Elo could be a therapeutic agent for MPN patients harboring JAK2V617F with MF.</p>

Journal

  • Rinsho Ketsueki

    Rinsho Ketsueki 61 (1), 3-10, 2020

    The Japanese Society of Hematology

Keywords

Details 詳細情報について

Report a problem

Back to top