AIDS-ASSOCIATED LYMPHOPROLIFERATIVE DISORDERS

艾滋病相关的淋巴增殖性疾病

• 批准号: 2089283
• 负责人: Riccardo Dalla-Favera
• 金额: $ 27.46万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-04-01 至 1997-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2089283
• 关键词: AIDS; B lymphocyte; Burkitt's lymphoma; Epstein Barr virus; Hodgkin's disease; Retroviridae disease; antigen receptors; antiviral antibody; athymic mouse; biopsy; cell differentiation; cell growth regulation; cell population study; cellular immunity; chronic leukemia; clone cells; cytogenetics; cytomegalovirus; enzyme linked immunosorbent assay; gene expression; gene mutation; gene rearrangement; genetic markers; human T cell lymphotropic virus type 1; human T cell lymphotropic virus type 2; human genetic material tag; human immunodeficiency virus; human tissue; immunofluorescence technique; immunoglobulin genes; in situ hybridization; leukocyte activation disorder; lymph nodes; lymphocytic leukemia; molecular pathology; neoplastic transformation; nucleic acid sequence; oncogenes; oncogenic virus; transfection; virus cytopathogenic effect; virus genetics; virus infection mechanism; virus protein; virus replication; western blottings

The general objective of this research project is to study the pathogenesis of AIDS-associated lymphoproliferative disorders including non-Hodgkin lymphoma (AIDS-NHL), Hodgkin disease (Aids- HD) and chronic lymphocytic leukemia (AIDS-CLL). We have identified clonal B-cell populations which are detectable in the lympho nodes of AIDS patients affected by the lymphadenopathy syndrome (LAS) and may represent premalignant populations. We have also determined that c-myc oncogene activation and Epstein-Barr Virus (EBV) infection are associated with AIDS-NHL development. Based on these findings the following lines of research will be pursued: 1) Isolation of clonal B-cell populations and characterization for stage of differentiation, growth requirements, presence and expression of EBV sequences, antibody production and reactivity against relevant viruses (HTLV-I, HTLV-II, HIV, CMV, EBV); 2) Molecular analysis of rearranged and unrearranged c-myc oncogene loci in AIDS-NHL to gain insight into the mechanism of activation; 3) testing the biological effects of c-myc oncogene introduced into the clonal B-cell population isolated in 1); 4) analysis of the role of EBV infection in EBV-positive AIDS-NHL cases; 5) molecular analysis of AIDS-HD and AIDS-CLL for clonality, presence of activated oncogenes (c-myc) and presence of relevant viral sequences (HTLV-I, HTLV-II, HIV, CMY, EBV).

该研究项目的一般目标是研究 艾滋病相关淋巴增生性疾病的发病机理 包括非霍奇金淋巴瘤（AIDS-NHL），霍奇金疾病（AIDS- HD）和慢性淋巴细胞性白血病（AIDS-CLL）。 我们有 确定的克隆B细胞种群，可在 受淋巴结病影响的艾滋病患者的淋巴结 综合征（LAS），可能代表prediment症的人群。 我们有 还确定了c-myc癌基因激活和爱泼斯坦 - 巴尔 病毒（EBV）感染与AIDS-NHL发育有关。 基于这些发现，以下研究线将是 追踪：1）隔离克隆人B细胞种群和 分化阶段，增长要求的表征， EBV序列的存在和表达，抗体产生和 针对相关病毒的反应性（HTLV-I，HTLV-II，HIV，CMV， EBV）; 2）重新排列和删除的C-MYC的分子分析 AIDS-NHL中的Oncogene基因座，以深入了解 激活; 3）测试c-myc癌基因的生物学作用 引入1）中分离的克隆B细胞种群； 4） 分析EBV感染在EBV阳性AIDS-NHL中的作用 案件； 5）AIDS-HD和AIDS-CLL分子分析克隆性， 存在激活的癌基因（C-MYC）和相关的存在 病毒序列（HTLV-I，HTLV-II，HIV，CMY，EBV）。