MOLECULAR EPIDEMIOLOGY OF AIDS-ASSOCIATED LYMPHOMA

艾滋病相关淋巴瘤的分子流行病学

• 批准号: 6172875
• 负责人: OTONIEL MARTINEZ-MAZA
• 金额: $ 28.45万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-30 至 2002-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6172875
• 关键词: AIDS related neoplasm /cancer; B cell lymphoma; Burkitt's lymphoma; CD antigens; Epstein Barr virus; Herpesviridae disease; biomarker; clinical research; gene rearrangement; human subject; immunoglobulin genes; molecular pathology; neoplasm /cancer epidemiology

DESCRIPTION (adapted from the Abstract): Non-Hodgkin's B-cell lymphoma is seen in greatly-elevated frequency in the acquired immunodeficiency syndrome (AIDS) and in infection with the human immunodeficiency virus (HIV). In this application, the Principal Investigator proposes studies to elucidate the molecular epidemiology of AIDS-lymphoma. In preliminary work, the Principal Investigator found that elevated serum levels of sCD23, as well as elevated levels of other immune system molecules (IgE, sCD27), precede the appearance of AIDS-lymphoma. Also, the elevated levels of sCD23 seen to precede AIDS-lymphoma may be due to the production of this molecule by tumor cells. In the proposed studies, the Investigator and associates will test the hypotheses that the over-expression of sCD23 (and other molecules) that precedes AIDS-lymphoma reflects: (1) immune dysfunction leading to B-cell hyper-activation and enhanced Ig isotype switching, perhaps contributing to the c-myc:Ig gene chromosomal translocation commonly seen in this cancer, or alternatively, (2) the production of these substances (sCD23 and other molecules) by the lymphoma cells themselves, or (3) reactivation of EBV infection. Also, they will examine the predictive value of the expression of these molecules for AIDS-lymphoma, and the expression of these molecules in lymphoma not associated with HIV infection, including African endemic Burkitt's lymphoma. Their specific aims are to: (1) define the pattern of expression of sCD23 prior to the emergence of AIDS-lymphoma; (2) determine/confirm which immune system molecules, other than sCD23, are elevated in those who develop AIDS-lymphoma; (3) determine if the measurement of serum levels of molecules other than sCD23 provides additional information for predicting the appearance of AIDS-lymphoma; and (4) determine if sCD23 or other immune system molecules are elevated in non-Hodgkin's B-cell lymphoma not associated with HIV infection, or in AIDS-lymphoma in hemophiliacs. The accomplishment of these specific aims will add valuable new information to our understanding of the molecular epidemiology of AIDS-lymphoma, as well as the role of immune dysfunction in the generation and growth of this cancer.

描述（改编自摘要）：非霍奇金 B 细胞淋巴瘤是 在获得性免疫缺陷综合征中出现频率大大升高 （艾滋病）和感染人类免疫缺陷病毒（HIV）。在 在此申请中，首席研究员提出研究来阐明 艾滋病淋巴瘤的分子流行病学。在前期工作中， 首席研究员发现 sCD23 的血清水平升高，以及 其他免疫系统分子（IgE、sCD27）水平升高，先于 艾滋病淋巴瘤的出现。此外，sCD23 水平升高 艾滋病淋巴瘤之前发生可能是由于肿瘤产生这种分子 细胞。在拟议的研究中，研究者和同事将测试 假设 sCD23（和其他分子）的过度表达 先于艾滋病-淋巴瘤反映出：（1）免疫功能障碍导致B细胞 过度激活和增强的 Ig 同种型转换，可能有助于 c-myc:Ig 基因染色体易位常见于这种癌症，或 或者，(2) 这些物质（sCD23 和其他物质）的生产 分子）由淋巴瘤细胞本身引起，或（3）EBV重新激活 感染。此外，他们还将检查表达式的预测价值 这些分子对艾滋病淋巴瘤的影响，以及这些分子的表达 与艾滋病毒感染无关的淋巴瘤，包括非洲流行病 伯基特淋巴瘤。他们的具体目标是：（1）定义模式 艾滋病淋巴瘤出现之前 sCD23 的表达； (2) 确定/确认除 sCD23 之外的哪些免疫系统分子 在患有艾滋病淋巴瘤的人中升高； (3) 判断是否 测量 sCD23 以外的分子的血清水平可提供 预测艾滋病淋巴瘤出现的额外信息；和 (4)确定sCD23或其他免疫系统分子是否升高 与 HIV 感染无关或与 HIV 感染无关的非霍奇金 B 细胞淋巴瘤 血友病患者的艾滋病淋巴瘤。这些具体目标的实现 将为我们对分子的理解添加有价值的新信息 艾滋病淋巴瘤的流行病学，以及免疫功能障碍在其中的作用 这种癌症的产生和生长。