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[滤泡性淋巴瘤发病机制的新发现及靶向治疗概念]

[Novel Findings in Follicular Lymphoma Pathogenesis and the Concepts of Targeted Therapy].

作者信息

Deván J, Musilová K, Janíková A, Mráz M

出版信息

Klin Onkol. 2017 Summer;30(4):247-257. doi: 10.14735/amko2017247.

Abstract

The molecular pathogenesis of follicular lymphoma (FL) was partially revealed by the discovery of BCL2 translocations to the region encoding the immunoglobulin heavy chain, which accompany the vast majority of cases. This aberration leads to the ectopic and constitutive expression of anti-apoptotic BCL2 protein in B-cells. Nevertheless, the aberration alone is not sufficient for FL development, which suggests necessity of further genetic aberrations acquisition for neoplastic transformation to FL. Their discovery has been enabled by recent progress in the field of massive parallel sequencing (next generation sequencing), which revealed high number of genetic aberrations connected with onset and progression of FL. The occurrence of many of these aberrations in the early stages of the disease, and the fact that they are shared by the majority of patients with FL, fundamentally changed our former understanding of the disease onset. Furthermore, in a large fraction of patients, FL undergoes histological transformation to a more aggressive lymphoma, which is also associated with specific genetic alterations. In this review, we summarize the current knowledge of molecular pathways connected with FL biology and discuss their role in the context of normal B-cell development. Understanding of FL biology is essential for the development of new targeted therapies and the stratification of patients, and potentially also for the selection of treatment for specific patients who share the same genetic aberrations.Key words: follicular lymphoma - mutation - aberration - apoptosis - epigenetic regulators - microRNA This research was carried out under the project CEITEC 2020 (LQ1601) with financial support from the Ministry of Education, Youth and Sports of the Czech Republic under the National Sustain ability Programme II. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 28. 1. 2017Accepted: 5. 3. 2017.

摘要

滤泡性淋巴瘤(FL)的分子发病机制部分是通过发现BCL2易位至编码免疫球蛋白重链的区域而得以揭示的,绝大多数病例都伴有这种情况。这种异常导致抗凋亡BCL2蛋白在B细胞中异位且持续表达。然而,仅这种异常并不足以引发FL的发展,这表明肿瘤转化为FL还需要获得进一步的基因异常。大规模平行测序(下一代测序)领域的最新进展使得这些异常得以发现,该进展揭示了大量与FL的发生和进展相关的基因异常。这些异常中有许多在疾病早期就已出现,并且大多数FL患者都存在这些异常,这从根本上改变了我们以前对疾病发病的认识。此外,在很大一部分患者中,FL会发生组织学转化,变为侵袭性更强的淋巴瘤,这也与特定的基因改变有关。在本综述中,我们总结了与FL生物学相关的分子途径的当前知识,并讨论了它们在正常B细胞发育背景下的作用。了解FL生物学对于开发新的靶向治疗方法和患者分层至关重要,甚至可能对于选择具有相同基因异常的特定患者的治疗方法也很重要。关键词:滤泡性淋巴瘤 - 突变 - 异常 - 凋亡 - 表观遗传调节因子 - 微小RNA 本研究是在项目CEITEC 2020(LQ1601)下进行的,由捷克共和国教育、青年和体育部在国家可持续发展计划II的资助下提供资金支持。作者声明他们在研究中使用的药物、产品或服务方面不存在潜在的利益冲突。编辑委员会声明该手稿符合ICMJE对生物医学论文的建议。提交日期:2017年1月28日 接受日期:2017年3月5日

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