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从全基因组关联研究追踪 B 细胞非霍奇金淋巴瘤的遗传易感性背景。

Tracking the Genetic Susceptibility Background of B-Cell Non-Hodgkin's Lymphomas from Genome-Wide Association Studies.

机构信息

Faculté de Médecine, Sorbonne Université, 75013 Paris, France.

Brain and Spine Institute (ICM), 75013 Paris, France.

出版信息

Int J Mol Sci. 2020 Dec 24;22(1):122. doi: 10.3390/ijms22010122.

Abstract

B-cell non-Hodgkin's lymphoma (NHL) risk associations had been mainly attributed to family history of the disease, inflammation, and immune components including human leukocyte antigen (HLA) genetic variations. Nevertheless, a broad range of genome-wide association studies (GWAS) have shed light into the identification of several genetic variants presumptively associated with B-cell NHL etiologies, survival or shared genetic risk with other diseases. The present review aims to overview HLA structure and diversity and summarize the evidence of genetic variations, by GWAS, on five NHL subtypes (diffuse large B-cell lymphoma DLBCL, follicular lymphoma FL, chronic lymphocytic leukemia CLL, marginal zone lymphoma MZL, and primary central nervous system lymphoma PCNSL). Evidence indicates that the HLA zygosity status in B-cell NHL might promote immune escape and that genome-wide significance variants can give biological insight but also potential therapeutic markers such as WEE1 in DLBCL. However, additional studies are needed, especially for non-DLBCL, to replicate the associations found to date.

摘要

B 细胞非霍奇金淋巴瘤(NHL)的风险关联主要归因于疾病家族史、炎症和免疫成分,包括人类白细胞抗原(HLA)的遗传变异。然而,广泛的全基因组关联研究(GWAS)已经揭示了一些遗传变异体,这些变异体可能与 B 细胞 NHL 的发病机制、生存或与其他疾病的共同遗传风险有关。本综述旨在概述 HLA 结构和多样性,并总结 GWAS 在五种 NHL 亚型(弥漫性大 B 细胞淋巴瘤 DLBCL、滤泡性淋巴瘤 FL、慢性淋巴细胞白血病 CLL、边缘区淋巴瘤 MZL 和原发性中枢神经系统淋巴瘤 PCNSL)中遗传变异的证据。有证据表明,B 细胞 NHL 中的 HLA 基因型状态可能促进免疫逃逸,全基因组意义显著的变异可以提供生物学见解,还可以提供潜在的治疗标志物,如 DLBCL 中的 WEE1。然而,还需要更多的研究,特别是对于非 DLBCL 患者,以复制迄今为止发现的关联。

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