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Role of BAFF/BAFF-R axis in B-cell non-Hodgkin lymphoma

机译:BAFF / BAFF-R轴在B细胞非霍奇金淋巴瘤中的作用

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摘要

B-cell activating factor (BAFF), as a member of the tumor necrosis factor (TNF) ligand family, plays important roles in B-cell homeostasis, tolerance, and malignancy. BAFF binds to three receptors of TNF, TACT, BCMA and BAFF-receptor (BAFF-R). In particular, the BAFF/BAFF-R pathway is crucial to the survival and growth of mature normal and malignant B-cells. BAFF is displayed on the cell surface or is released in a soluble form after cleavage from the plasma membrane. BAFF-R as the main BAFF receptor is expressed mainly on B-cells. Aberrant BAFF expression was found in malignant B-cells from B-cell non-Hodgkin lymphoma (B-NHL) patients, which protects these cells from spontaneous or drug-induced apoptosis and stimulated NF-kappa B activation via autocrine and/or paracrine pathways. However, the mechanisms involved in the gene expression and regulation of BAFF or BAFF-R has not been elucidated. More importantly, the design of reagents able to counteract BAFF/BAFF-R pathways may be of therapeutic value for B-NHL. Results of ongoing clinical trials with BAFF or BAFF-R antagonists are eagerly awaited. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
机译:B细胞活化因子(BAFF)作为肿瘤坏死因子(TNF)配体家族的成员,在B细胞稳态,耐受性和恶性肿瘤中起着重要作用。 BAFF与TNF,TACT,BCMA和BAFF受体(BAFF-R)的三个受体结合。特别地,BAFF / BAFF-R途径对于成熟的正常和恶性B细胞的存活和生长至关重要。 BAFF显示在细胞表面上或从质膜上裂解后以可溶形式释放。作为主要BAFF受体的BAFF-R主要在B细胞上表达。在B细胞非霍奇金淋巴瘤(B-NHL)患者的恶性B细胞中发现了异常的BAFF表达,它可以保护这些细胞免于自发或药物诱导的凋亡,并通过自分泌和/或旁分泌途径刺激NF-κB活化。 。然而,尚未阐明涉及BAFF或BAFF-R的基因表达和调控的机制。更重要的是,能够抵消BAFF / BAFF-R途径的试剂的设计对于B-NHL可能具有治疗价值。迫切期待BAFF或BAFF-R拮抗剂正在进行的临床试验结果。 (C)2014 Elsevier Ireland Ltd.保留所有权利。

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