原发性积液性淋巴瘤的可用药宿主基因依赖性

IF 5.7 2区 医学 Q1 VIROLOGY
Neil Kuehnle, Eva Gottwein
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引用次数: 1

摘要

卡波西肉瘤相关疱疹病毒(KSHV)引起原发性积液性淋巴瘤(PEL)。在这里,我们回顾了人类基因在pel衍生细胞系中的重要性。我们基于改进的人类癌症类型核心必需基因的定义,提供了一个更新的pel特异性人类基因依赖列表。PEL细胞系对干扰素调节因子4 (IRF4)、碱性白细胞拉环atf样转录因子(BATF)、G1/S周期蛋白D2 (CCND2)、CASP8和FADD样细胞凋亡调节剂(CFLAR)、MCL1细胞凋亡调节剂(MCL1)和小鼠双分钟2 (MDM2)的需求已被实验证实。KSHV选择IRF4和BATF来驱动超增强子(SE)介导的IRF4自身、MYC和CCND2的表达。Epstein-Barr病毒转化的淋巴母细胞样细胞系(LCLs)和人t细胞白血病病毒1型转化的成人t细胞白血病/淋巴瘤(ATLL)细胞系以及几种非病毒病因的b细胞淋巴瘤都具有IRF4对se介导的基因表达的依赖性。lcl和ATLL细胞系与PEL相似地共享对CCND2和CFLAR的依赖,但也具有不同的基因依赖性。遗传依赖性可用于前列腺癌和其他癌症的治疗干预。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Druggable host gene dependencies in primary effusion lymphoma

Kaposi’s sarcoma-associated herpesvirus (KSHV) causes primary effusion lymphoma (PEL). Here, we review what is known about human gene essentiality in PEL-derived cell lines. We provide an updated list of PEL-specific human gene dependencies, based on the improved definition of core essential genes across human cancer types. The requirements of PEL cell lines for interferon regulatory factor 4 (IRF4), basic leukine zipper ATF-like transcription factor (BATF), G1/S cyclin D2 (CCND2), CASP8 and FADD like apoptosis regulator (CFLAR), MCL1 apoptosis regulator (MCL1), and murine double minute 2 (MDM2) have been confirmed experimentally. KSHV co-opts IRF4 and BATF to drive superenhancer (SE)-mediated expression of IRF4 itself, MYC, and CCND2. IRF4 dependency of SE-mediated gene expression is shared with Epstein–Barr virus-transformed lymphoblastoid cell lines (LCLs) and human T-cell leukemia virus type 1-transformed adult T-cell leukemia/lymphoma (ATLL) cell lines, as well as several B-cell lymphomas of nonviral etiology. LCLs and ATLL cell lines similarly share dependencies on CCND2 and CFLAR with PEL, but also have distinct gene dependencies. Genetic dependencies could be exploited for therapeutic intervention in PEL and other cancers.

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来源期刊
CiteScore
11.80
自引率
5.10%
发文量
76
审稿时长
83 days
期刊介绍: Current Opinion in Virology (COVIRO) is a systematic review journal that aims to provide specialists with a unique and educational platform to keep up to date with the expanding volume of information published in the field of virology. It publishes 6 issues per year covering the following 11 sections, each of which is reviewed once a year: Emerging viruses: interspecies transmission; Viral immunology; Viral pathogenesis; Preventive and therapeutic vaccines; Antiviral strategies; Virus structure and expression; Animal models for viral diseases; Engineering for viral resistance; Viruses and cancer; Virus vector interactions. There is also a section that changes every year to reflect hot topics in the field.
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