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

描述（由申请人提供）：大约90%的健康成年人感染eb病毒（EBV），但在艾滋病患者中，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，促进细胞增殖，抑制细胞凋亡；这表明它在肿瘤发生中的作用可能导致艾滋病患者弥漫性大B细胞淋巴瘤（DLBCL）和其他非霍奇金淋巴瘤的发病率高出60倍。支持这一观点的是，艾滋病患者的dlbcl中几乎100%存在EBV，但在非免疫功能低下患者的dlbcl中仅约3%存在EBV。我们的项目是基于EBV+艾滋病患者比非免疫功能低下患者需要更少的细胞基因组变化来发展为DLBCL的期望。利用来自DLBCL患者活组织检查的体内转录组和遗传信息，我们将使用一种策略来确定患有和不患有艾滋病的DLBCL患者的不同癌症途径。这很重要，因为它将突出共同和独特的途径，可用于指导治疗方法的发展，以适当有效地对抗这些亚型的dlbcl。

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.