George Washington University Cancer Center, Washington DC, USA.
Department of Medicine A, Hematology, Oncology and Pneumology, University Hospital Münster, Münster, Germany; Cluster of Excellence EXC 1003, Cells in Motion, Münster, Germany.
Cancer Treat Rev. 2018 Apr;65:41-46. doi: 10.1016/j.ctrv.2018.01.002. Epub 2018 Feb 1.
Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous diagnostic category with different molecular subtypes defined by distinct gene expression patterns and divergent mechanisms of oncogenic activation. Several studies have suggested an inferior survival for patients of the activated B-cell-like (ABC) versus the germinal center B-cell-like (GCB) DLBCL subtype which has led to increasing interest in investigating pharmacological inhibition of signaling pathways which contribute to lymphomagenesis and that are specifically utilized by ABC DLBCL cells. One of these signaling cascades is the B-cell receptor (BCR) pathway and several approaches in clinical trials to target this cascade have demonstrated promising therapeutic activity. This review discusses our current understanding of the role of BCR signaling in different DLBCL subtypes, including primary central nervous system lymphoma (PCNSL), a subgroup of DLBCL that is particularly dependent on BCR signaling. One specific aim of this review is to highlight novel approaches to therapeutically target BCR signaling in DLBCL.
弥漫性大 B 细胞淋巴瘤（DLBCL）是一种具有不同分子亚型的异质性诊断类别，其通过不同的基因表达模式和不同的致癌激活机制来定义。一些研究表明，活化 B 细胞样（ABC）与生发中心 B 细胞样（GCB）DLBCL 亚型的患者生存情况较差，这导致人们越来越关注研究针对导致淋巴瘤发生和 ABC DLBCL 细胞特异性利用的信号通路的药理学抑制。这些信号级联中的一个是 B 细胞受体（BCR）途径，临床试验中针对该级联的几种方法已经证明具有有前途的治疗活性。这篇综述讨论了我们目前对 BCR 信号在不同 DLBCL 亚型中的作用的理解，包括原发性中枢神经系统淋巴瘤（PCNSL），这是一种特别依赖于 BCR 信号的 DLBCL 亚组。本篇综述的一个特定目的是强调针对 DLBCL 中 BCR 信号的治疗靶标的新方法。
