B-cell activating factor in the pathophysiology of multiple myeloma: a target for therapy?
B-cell activating factor in the pathophysiology of multiple myeloma: a target for therapy?
复制标题
DOI：
10.1038/bcj.2015.3
复制
发表时间：
2015-02-27
影响因子：
12.8
通讯作者：
Kersten MJ
中科院分区：
文献类型：
--
作者：
Hengeveld PJ;Kersten MJ
多发性骨髓瘤（MM）是目前无法治愈的浆细胞恶性肿瘤。恶性骨髓瘤细胞（MMC）的生存严重依赖于骨髓（BM）微环境。这种肿瘤微环境的一个组成部分，B细胞激活因子（BAFF），已经被认为是这种相互作用的关键参与者。这篇综述讨论了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作为MMCs的生存因子发挥作用。此外，MMC表达几种BAFF结合受体。其中，只有跨膜激活物和CAML相互作用物（TACI）与MMC连接BAFF的能力相关。此外，TACI的表达水平与MMC的BM依赖性水平相关。MMCs上BAFF受体的连接导致κ-B核因子（NF-κB）途径的激活，这是许多B细胞恶性肿瘤发病机制的关键途径。与健康对照相比，MM患者的血清BAFF水平显著升高，并与总生存期呈负相关。因此，BAFF信号传导是MM治疗的一个有趣的靶点。目前正在评估几种BAFF抑制药物用于MM治疗。这些药物包括BAFF单克隆抗体（tabalumab）和抗体-药物偶联物（GSK 2857916）。
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).