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

描述(由申请人提供)：大约90%的健康成年人感染了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额外的EBV蛋白表达(III型潜伏期)。这些病毒蛋白改变CEL信号以驱动增殖和抑制凋亡；这表明在肿瘤形成中发挥了作用，这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增加60倍。支持这一观点的是，在艾滋病患者的DLBCL中，几乎100%的DLBCL中都存在EBV，但在免疫未受损的患者中，只有大约3%的DLBCL中存在EBV。我们的项目是基于这样的期望，即EBV+艾滋病患者比非免疫低下患者需要更少的细胞基因组变化就可以发展为DLBCL。利用体内转录组和来自DLBCL患者活检组织的遗传信息，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。这一点很重要，因为它将突出共同和独特的途径，可用于指导开发对这些亚类DLBCL适当有效的治疗方法。

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.