文章：

Semaphorin 4D与新诊断的多发性骨髓瘤患者骨吸收增加、高钙血症及疾病分期相关

Semaphorin 4D correlates with increased bone resorption, hypercalcemia, and disease stage in newly diagnosed patients with multiple myeloma

原文发布日期：2018-05-11

DOI: 10.1038/s41408-018-0075-6

类型: Article

开放获取: 是

英文摘要：

Multiple myeloma (MM) is characterized by bone destruction due to increased bone resorption and decreased bone formation. Semaphorin 4D (CD100, Sema4D) is expressed by osteoclasts, binds to its receptor Plexin-B1, and acts as a mediator of osteoclast–osteoblast interaction that ultimately inhibits osteoblastic bone formation. Preclinical data suggest that Sema4D/Plexin-B1 pathway is implicated in MM-induced bone disease. However, there is no information on the role of Sema4D in MM patients. Thus, we evaluated Sema4D and Plexin-B1 in six myeloma cells lines in vitro; in the bone marrow plasma (BMP) and serum of 72 newly diagnosed symptomatic MM (NDMM) patients and in 25 healthy controls. Only one myeloma cell line produced high Sema4D. BMP and circulating Sema4D and Plexin-B1 levels were significantly higher in MM patients compared to controls (p < 0.01). Sema4D correlated with serum calcium levels (p < 0.001), increased bone resorption (as assessed by CTX; p < 0.01), and ISS (p < 0.001). There was a trend for higher Sema4D levels in patients with osteolysis (p = 0.07), while patients with diffuse MRI pattern had higher BMP Sema4D levels (p = 0.02). Our data suggest that Sema4D is elevated in MM patients and correlate with adverse myeloma features and increased bone resorption, providing a possible target for novel therapeutic approaches in MM.

摘要翻译： 

多发性骨髓瘤（MM）的特征是骨吸收增强伴随骨形成减弱导致的骨质破坏。破骨细胞表达的信号素4D（CD100，Sema4D）与其受体丛状蛋白B1结合，作为破骨细胞-成骨细胞相互作用的介质，最终抑制成骨细胞的骨形成功能。临床前数据表明Sema4D/Plexin-B1通路参与MM诱导的骨病发生。然而目前尚无Sema4D在MM患者中作用的相关研究。为此，我们通过体外实验评估了六株骨髓瘤细胞系、72例新诊断有症状MM（NDMM）患者及25例健康对照者的骨髓血浆（BMP）和血清中Sema4D与Plexin-B1的表达水平。仅有一株骨髓瘤细胞系呈现高Sema4D表达。MM患者BMP及循环系统中的Sema4D和Plexin-B1水平均显著高于对照组（p < 0.01）。Sema4D与血清钙水平（p < 0.001）、骨吸收增强标志物CTX（p < 0.01）及国际分期系统（ISS）分期（p < 0.001）呈正相关。骨溶解患者中Sema4D水平有升高趋势（p = 0.07），而MRI弥漫性病变患者的BMP Sema4D水平显著更高（p = 0.02）。本研究数据表明Sema4D在MM患者中升高，且与不良疾病特征及骨吸收增强相关，为MM的新治疗策略提供潜在靶点。

原文链接：

Semaphorin 4D correlates with increased bone resorption, hypercalcemia, and disease stage in newly diagnosed patients with multiple myeloma