MOLECULAR EPIDEMIOLOGY OF AIDS-ASSOCIATED LYMPHOMA

描述(摘自摘要)：非霍奇金B细胞淋巴瘤 在获得性免疫缺陷综合征中出现的频率大大增加 (艾滋病)和感染人类免疫缺陷病毒(艾滋病毒)。在……里面 这项申请，首席调查员提出研究，以澄清 艾滋病--淋巴瘤的分子流行病学。在前期工作中， 主要研究人员发现，血清sCD23水平升高，以及 其他免疫系统分子(IgE，sCD27)水平升高，先于 艾滋病的出现--淋巴瘤。此外，sCD23水平的升高被认为是 先于艾滋病-淋巴瘤可能是由于肿瘤产生这种分子所致 细胞。在拟议的研究中，调查员和同事将测试 假设sCD23(和其他分子)的过度表达 艾滋病的先兆-淋巴瘤反映：(1)免疫功能障碍导致B细胞 过度激活和增强的Ig同型转换，可能有助于 C-myc：IG基因染色体易位在此癌中常见，或 或者，(2)这些物质的生产(sCD23和其他 分子)或(3)EBV的重新激活 感染。此外，他们还将检查表达式的预测值 这些分子对艾滋病-淋巴瘤的作用，以及这些分子的表达 与艾滋病毒感染无关的淋巴瘤，包括非洲地方病 伯基特淋巴瘤。他们的具体目标是：(1)确定 SCD23在艾滋病淋巴瘤发生前的表达； 确定/确认除sCD23以外的免疫系统分子 在患上艾滋病-淋巴瘤的人中升高；(3)确定是否 对血清中sCD23以外的分子水平的测量提供了 用于预测艾滋病-淋巴瘤出现的其他信息；以及 (4)确定sCD23或其他免疫系统分子是否在 非霍奇金B细胞淋巴瘤与艾滋病毒感染无关，或在 艾滋病--血友病患者中的淋巴瘤。这些具体目标的实现 将为我们对分子的理解增加有价值的新信息 艾滋病-淋巴瘤的流行病学，以及免疫功能障碍在 这种癌症的产生和发展。

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.