文章：

B细胞活化因子在多发性骨髓瘤病理生理中的作用：治疗的靶点？

B-cell activating factor in the pathophysiology of multiple myeloma: a target for therapy?

原文发布日期：2015-02-27

DOI: 10.1038/bcj.2015.3

类型: Review

开放获取: 是

英文摘要：

Multiple myeloma (MM) is a currently incurable malignancy of plasma cells. Malignant myeloma cells (MMCs) are heavily dependent upon the bone marrow (BM) microenvironment for their survival. One component of this tumor microenvironment, B-Cell Activating Factor (BAFF), has been implicated as a key player in this interaction. This review discusses the role of BAFF in the pathophysiology of MM, and the potential of BAFF-inhibitory therapy for the treatment of MM. Multiple studies have shown that BAFF functions as a survival factor for MMCs. Furthermore, MMCs express several BAFF-binding receptors. Of these, only Transmembrane Activator and CAML Interactor (TACI) correlates with the MMC’s capability to ligate BAFF. Additionally, the level of expression of TACI correlates with the level of the MMC’s BM dependency. Ligation of BAFF receptors on MMCs causes activation of the Nuclear Factor of κ-B (NF-κB) pathway, a crucial pathway for the pathogenesis of many B-cell malignancies. Serum BAFF levels are significantly elevated in MM patients when compared to healthy controls, and correlate inversely with overall survival. BAFF signaling is thus an interesting target for the treatment of MM. Several BAFF-inhibitory drugs are currently under evaluation for the treatment of MM. These include BAFF-monoclonal antibodies (tabalumab) and antibody-drug conjugates (GSK2857916).

摘要翻译： 

多发性骨髓瘤（MM）是一种目前无法治愈的浆细胞恶性肿瘤。恶性骨髓瘤细胞（MMCs）的存活高度依赖于骨髓（BM）微环境。B细胞活化因子（BAFF）作为该肿瘤微环境的重要组成部分，在这种相互作用中发挥着关键作用。本篇综述探讨BAFF在MM病理生理学中的作用，以及BAFF抑制疗法治疗MM的潜力。多项研究表明，BAFF可作为MMCs的生存因子。此外，MMCs表达多种BAFF结合受体，其中仅跨膜激活剂及CAML相互作用因子（TACI）与MMCs结合BAFF的能力相关。值得注意的是，TACI的表达水平与MMCs对骨髓微环境的依赖程度呈正相关。BAFF受体与MMCs结合后会激活核因子κB（NF-κB）通路——这是许多B细胞恶性肿瘤发病机制中的关键通路。与健康对照组相比，MM患者血清BAFF水平显著升高，且与总体生存率呈负相关。因此BAFF信号通路成为治疗MM的潜在靶点。目前已有多种BAFF抑制剂正在评估中，包括BAFF单克隆抗体（塔巴木单抗）和抗体-药物偶联物（GSK2857916）。

原文链接：

B-cell activating factor in the pathophysiology of multiple myeloma: a target for therapy?