Role of neoplastic monocyte-derived fibrocytes in primary myelofibrosis.
Role of neoplastic monocyte-derived fibrocytes in primary myelofibrosis.
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DOI：
10.1084/jem.20160283
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发表时间：
2016-08-22
期刊：
影响因子：
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通讯作者：
Estrov Z
中科院分区：
文献类型：
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作者：
Verstovsek S;Manshouri T;Pilling D;Bueso-Ramos CE;Newberry KJ;Prijic S;Knez L;Bozinovic K;Harris DM;Spaeth EL;Post SM;Multani AS;Rampal RK;Ahn J;Levine RL;Creighton CJ;Kantarjian HM;Estrov Z
Estrov和合作者研究了纤维细胞在原发性骨髓纤维化中的作用，并提出了一种新的治疗方法。原发性骨髓纤维化（PMF）是一种致命的肿瘤疾病，以克隆性骨髓增生和进行性骨髓纤维化为特征，被认为是由过度产生的生长因子刺激间充质基质细胞诱导的。然而，其他疾病的组织纤维化与单核细胞来源的纤维细胞有关。因此，我们试图确定纤维细胞是否在PMF中诱导BM纤维化中起作用。在这项研究中，我们发现PMF患者的骨髓中含有丰富的克隆性、肿瘤性胶原蛋白和纤维连接蛋白生成纤维细胞。移植骨髓纤维化患者骨髓细胞的免疫缺陷小鼠表现出致命的骨髓纤维化样表型。用纤维细胞抑制剂血清淀粉样蛋白P （SAP; pentaxin -2）治疗异种移植物小鼠可显著延长存活时间，减缓骨髓纤维化的发展。总的来说，我们的数据表明肿瘤纤维细胞有助于PMF中BM纤维化的诱导，而用SAP抑制纤维细胞分化可能会干扰这一过程。
Estrov and collaborators examine the role of fibrocytes in primary myelofibrosis and propose a novel therapeutic approach. Primary myelofibrosis (PMF) is a fatal neoplastic disease characterized by clonal myeloproliferation and progressive bone marrow (BM) fibrosis thought to be induced by mesenchymal stromal cells stimulated by overproduced growth factors. However, tissue fibrosis in other diseases is associated with monocyte-derived fibrocytes. Therefore, we sought to determine whether fibrocytes play a role in the induction of BM fibrosis in PMF. In this study, we show that BM from patients with PMF harbors an abundance of clonal, neoplastic collagen- and fibronectin-producing fibrocytes. Immunodeficient mice transplanted with myelofibrosis patients’ BM cells developed a lethal myelofibrosis-like phenotype. Treatment of the xenograft mice with the fibrocyte inhibitor serum amyloid P (SAP; pentraxin-2) significantly prolonged survival and slowed the development of BM fibrosis. Collectively, our data suggest that neoplastic fibrocytes contribute to the induction of BM fibrosis in PMF, and inhibiting fibrocyte differentiation with SAP may interfere with this process.