EBV-mediated carcinogenesis in AIDS-associated Diffuse Large B Cell Lymphoma

EBV 介导的 AIDS 相关弥漫性大 B 细胞淋巴瘤的致癌作用

• 批准号: 8596646
• 负责人: Christina M O'Grady
• 金额: $ 4.03万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8596646
• 关键词: AIDS Malignancy Consortium; Acquired Immunodeficiency Syndrome; Adult; Apoptosis; Biopsy; Cancer Etiology; Community Clinical Oncology Program; Cytotoxic T-Lymphocytes; Data; Development; Documentation; EBV-associated malignancy; Epstein-Barr Virus Infections; Gene Expression; Gene Expression Profile; General Population; Genes; Genetic; Genome; Gold; Human Herpesvirus 4; Immunocompromised Host; Incidence; Malignant Neoplasms; Mediating; Minority-Based Community Clinical Oncology Program; Molecular Profiling; Mutation; Non-Hodgkin' s Lymphoma; Nucleotides; Oncogenic; Pathway interactions; Patients; Physicians; Plant Roots; RNA Sequences; Research; Role; Sampling; Signal Pathway; Signal Transduction; Specimen; System; Tumor Suppressor Proteins; Validation; Variant; Viral Proteins; Work; cancer genome; cancer specimen resource; carcinogenesis; expectation; fusion gene; genetic analysis; in vivo; insertion/deletion mutation; large cell Diffuse non-Hodgkin' s lymphoma; overexpression; patient population; public health relevance; repaired; response; standard care; therapeutic development; therapeutic target; transcriptome sequencing; tumor; tumorigenesis

DESCRIPTION (provided by applicant): Approximately 90% of healthy adults are infected with Epstein Barr Virus (EBV), but in AIDS patients the diminished cytotoxic T lymphocyte response allows the expression of additional EBV proteins (type III latency). These viral proteins alter cel signaling to drive proliferation and inhibit apoptosis; suggesting a role in tumorigenesis that could contribute to the ¿60-fold higher rate of Diffuse Large B Cell Lymphoma (DLBCL) and other Non-Hodgkin's Lymphomas in AIDS patients. Supporting this idea, EBV is present in nearly 100% of DLBCLs in AIDS patients, but only about 3% of DLBCLs in patients who are not immunocompromised. Our project is guided by the expectation that EBV+ AIDS patients require fewer changes in the cellular genome than non-immunocompromised patients to develop DLBCL. Using in vivo transcriptome and genetic information derived from DLBCL patient biopsies, we will use a strategy to determine the distinct cancer pathways in DLBCL patients with and without AIDS. This is important because it will highlight common and unique pathways that can be used to guide the development of therapeutics that are appropriately effective against these subclasses of DLBCLs.

描述（由申请人提供）：大约90%的健康成人感染了爱泼斯坦巴尔病毒（EBV），但在AIDS患者中，细胞毒性T淋巴细胞反应减弱，允许表达额外的EBV蛋白（III型潜伏期）。这些病毒蛋白改变细胞信号以驱动增殖和抑制凋亡;这表明在肿瘤发生中的作用可能导致艾滋病患者中弥漫性大B细胞淋巴瘤（DLBCL）和其他非霍奇金淋巴瘤的发病率高出约60倍。支持这一观点的是，EBV存在于艾滋病患者近100%的DLBCL中，但在非免疫功能低下的患者中仅约3%的DLBCL中。我们的项目是由这样的期望指导的，即EBV+ AIDS患者比非免疫功能低下的患者需要更少的细胞基因组变化来发展DLBCL。利用来自DLBCL患者活检的体内转录组和遗传信息，我们将使用一种策略来确定DLBCL患者伴和不伴AIDS的不同癌症途径。这很重要，因为它将突出可用于指导对DLBCL的这些亚类适当有效的治疗剂的开发的共同和独特的途径。