Gascoyne Duncan M, Banham Alison H
a Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine , University of Oxford , Oxford , UK.
Leuk Lymphoma. 2017 May;58(5):1037-1051. doi: 10.1080/10428194.2016.1228932. Epub 2016 Sep 27.
Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of mature B-cell lymphoma. While the majority of patients are cured with immunochemotherapy incorporating the anti-CD20 monoclonal antibody rituximab (R-CHOP), relapsed and refractory patients still have a dismal prognosis. DLBCL subtypes including an aggressive activated B-cell-like (ABC) and a more favorable prognosis germinal center-like (GCB) DLBCL have been identified by gene expression profiling and are characterized by distinct genetic abnormalities and oncogenic pathways. This identification of novel molecular targets is now enabling clinical trials to evaluate more effective personalized approaches to DLBCL therapy. The forkhead transcription factor FOXP1 is highly expressed in the ABC-DLBCL gene signature and has been extensively studied within the context of DLBCL for more than a decade. Here, we review the significance of FOXP1 in the pathogenesis of DLBCL, summarizing data supporting its utility as a prognostic and subtyping marker, its targeting by genetic aberrations, the importance of specific isoforms, and emerging data demonstrating a functional role in lymphoma biology. FOXP1 is one of the critical transcription factors whose deregulated expression makes important contributions to DLBCL pathogenesis. Thus, FOXP1 warrants further study as a potential theranostic in ABC-DLBCL.
弥漫性大B细胞淋巴瘤(DLBCL)是成熟B细胞淋巴瘤最常见的亚型。虽然大多数患者通过包含抗CD20单克隆抗体利妥昔单抗的免疫化疗(R-CHOP)得以治愈,但复发和难治性患者的预后仍然很差。通过基因表达谱分析已鉴定出DLBCL的亚型,包括侵袭性活化B细胞样(ABC)和预后较好的生发中心样(GCB)DLBCL,其特征是具有不同的基因异常和致癌途径。这种新分子靶点的鉴定现在使得临床试验能够评估更有效的DLBCL个性化治疗方法。叉头转录因子FOXP1在ABC-DLBCL基因特征中高度表达,并且在DLBCL的背景下已经被广泛研究了十多年。在这里,我们综述了FOXP1在DLBCL发病机制中的意义,总结了支持其作为预后和亚型标志物的效用的数据、其被基因畸变靶向的情况、特定异构体的重要性以及表明其在淋巴瘤生物学中具有功能作用的新出现的数据。FOXP1是关键转录因子之一,其表达失调对DLBCL发病机制有重要贡献。因此,FOXP1作为ABC-DLBCL潜在的诊疗靶点值得进一步研究。