文章：

高浓度骨膜蛋白与新诊断的有症状多发性骨髓瘤患者骨折发生率增加、MRI弥漫性改变、骨重塑异常及疾病晚期相关

High levels of periostin correlate with increased fracture rate, diffuse MRI pattern, abnormal bone remodeling and advanced disease stage in patients with newly diagnosed symptomatic multiple myeloma

原文发布日期：2016-10-07

DOI: 10.1038/bcj.2016.90

类型: Original Article

开放获取: 是

英文摘要：

Periostin is an extracellular matrix protein that is implicated in the biology of normal bone remodeling and in different cancer cell growth and metastasis. However, there is no information on the role of periostin in multiple myeloma (MM). Thus, we evaluated periostin in six myeloma cell lines in vitro; in the bone marrow plasma and serum of 105 newly diagnosed symptomatic MM (NDMM) patients and in the serum of 23 monoclonal gammopathy of undetermined significance (MGUS), 33 smoldering MM (SMM) patients, 30 patients at the plateau phase post-first-line therapy, 30 patients at first relapse and 30 healthy controls. We found high levels of periostin in the supernatants of myeloma cell lines compared with ovarian cancer cell lines that were not influenced by the incubation with the stromal cell line HS5. In NDMM patients the bone marrow plasma periostin was almost fourfold higher compared with the serum levels of periostin and correlated with the presence of fractures and of diffuse magnetic resonance imaging pattern of marrow infiltration. Serum periostin was elevated in NDMM patients compared with healthy controls, MGUS and SMM patients and correlated with advanced disease stage, high lactate dehydrogenase, increased activin-A, increased bone resorption and reduced bone formation. Patients at first relapse had also elevated periostin compared with healthy controls, MGUS and SMM patients, while even patients at the plateau phase had elevated serum periostin compared with healthy controls. These results support an important role of periostin in the biology of myeloma and reveal periostin as a possible target for the development of antimyeloma drugs.

摘要翻译： 

骨膜素是一种细胞外基质蛋白，参与正常骨改建生物学过程以及多种癌细胞的生长和转移。然而，关于骨膜素在多发性骨髓瘤中的作用尚无明确信息。为此，我们在体外对6个骨髓瘤细胞系中的骨膜素进行了评估；检测了105名新诊断症状性多发性骨髓瘤患者的骨髓血浆与血清、23名意义未明的单克隆丙种球蛋白血症患者、33名隐匿性多发性骨髓瘤患者、30名首次治疗後平台期患者、30名首次复发患者以及30名健康对照者的血清样本。研究发现，与卵巢癌细胞系相比，骨髓瘤细胞系上清液中的骨膜素水平较高，且不受基质细胞系HS5培养的影响。新诊断多发性骨髓瘤患者的骨髓血浆骨膜素水平较其血清骨膜素高出近四倍，并与骨折的存在及磁共振成像显示的弥漫性骨髓浸润模式相关。与健康对照组、意义未明的单克隆丙种球蛋白血症和隐匿性多发性骨髓瘤患者相比，新诊断患者的血清骨膜素升高，且与疾病晚期、高乳酸脱氢酶、激活素A增加、骨吸收增强及骨形成减少相关。首次复发患者的骨膜素水平也高于健康对照组、意义未明的单克隆丙种球蛋白血症和隐匿性多发性骨髓瘤患者，甚至平台期患者的血清骨膜素仍高于健康对照组。这些结果证实了骨膜素在骨髓瘤生物学中的重要作用，揭示了骨膜素可能作为抗骨髓瘤药物开发的潜在靶点。

原文链接：

High levels of periostin correlate with increased fracture rate, diffuse MRI pattern, abnormal bone remodeling and advanced disease stage in patients with newly diagnosed symptomatic multiple myeloma