IMMUNOLOGIC ANALYSIS OF PREMALIGNANT & MALIGNANT B-CELLS

癌前病变的免疫学分析

• 批准号: 3117344
• 负责人: George N. ABRAHAM
• 金额: $ 15.15万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-08-01 至 1991-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3117344
• 关键词: B lymphocyte; Epstein Barr virus; aging; antiidiotype antibody; cell mediated cytotoxicity; cryoglobulins; gammopathy; gel electrophoresis; gene expression; human age group; human subject; immunochemistry; immunoglobulin G; immunoglobulin M; ion exchange chromatography; molecular pathology; molecular sieving; oncogenes; plasmacytic leukemia; preneoplastic state

The monoclonal gammopathies are naturally occuring human B-cell disorders of Ig synthesis predominantly of elderly humans. Because of a high incidence of transformation into frank malignant lymphoproliferation they may be considered as premalignant diseases. Two such gammopathies are the mixed IgM-IgG and monoclonal IgG, cryoglobulinemias. The basis for the malignant transition in these disorders is unknown. However, prospective studies at the protein and cellular levels of patients in early stages of their disease, and patients whose diseases are becoming more aggressive and are clinically in a benign to malignant transition, should provide interesting information concerning the development of malignancy. Since these diseases involve the elderly, the ontologic and evolutionary expression, regulation, and gene changes of a normal light chain marker with nearly a 100% involvement in the mixed IgM-IgG cryoglobulinemias will be studies in healthy young, middle-aged, and older volunteers to clarify the basis of its involvement in this disease. In patients with the both types of cryoglobulinemia the changes which develop at the cellular level in the genes and in the gene product i.e. the cryoglobulins, will be studied prospectively in order to detect aberrations which would signal the development of malignancy. In these experiments transforming gene presence and activation, possible gross immunoglobulin gene rearrangements, comparative protein synthetic rates at the cellular level for normal Ig and cryoglobulin Ig, and the detection of mutated protein structure will be studied. As a final goal, the cellular presence and localization of the gene product which has been translocated to and replaced, the variable region of an immunoglobulin lambda light chain during the transition from a monoclonal IgG cryoglobulinemia to a plasma cell leukemia will be studied. Cumulatively the studies provide an ideal human disease model for study of the influence of aging and aberrant immunoglobulin synthesis on the development of B-cell malignancies.

单克隆丙种球蛋白病是自然发生的人类 B 细胞 Ig 合成障碍主要发生于老年人。 因为转变为坦率的发生率很高 恶性淋巴增殖，它们可能被认为是 癌前疾病。 两种这样的丙种球蛋白病是混合的 IgM-IgG 和单克隆 IgG，冷球蛋白血症。 的基础 这些疾病的恶性转变尚不清楚。 然而，蛋白质和细胞水平的前瞻性研究 处于疾病早期阶段的患者以及患者 他们的疾病变得更具侵袭性并且临床上 在良性到恶性的转变中，应该提供有趣的 有关恶性肿瘤发展的信息。 自从 这些疾病涉及老年人、本体论和 进化表达、调控和基因变化 正常轻链标记几乎 100% 参与 混合 IgM-IgG 冷球蛋白血症将在健康人群中进行研究 青年、中年、老年志愿者明确依据 其参与这种疾病。 对于同时患有这两种疾病的患者 冷球蛋白血症的类型 发生的变化 基因和基因产物的细胞水平，即 冷球蛋白，将进行前瞻性研究，以检测 预示着恶性肿瘤发展的畸变。 在这些改变基因存在和激活的实验中， 可能的总体免疫球蛋白基因重排，比较 正常 Ig 和 细胞水平的蛋白质合成率 冷球蛋白Ig和突变蛋白结构的检测 将被研究。 作为最终目标，细胞的存在和 已转位的基因产物的定位 并替换为免疫球蛋白 lambda 的可变区 从单克隆 IgG 转变过程中的轻链 将研究冷球蛋白血症至浆细胞白血病。 这些研究累计提供了理想的人类疾病模型 用于研究衰老和异常免疫球蛋白的影响 合成对 B 细胞恶性肿瘤发展的影响。