VIRAL MALIGNANT LYMPHOMAGENESIS

病毒恶性淋巴瘤发生

• 批准号: 3171920
• 负责人: Martin nmi Haas
• 金额: $ 27.75万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-05-01 至 1992-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3171920
• 关键词: Retroviridae disease; T lymphocyte; X ray; bone marrow; cell sorting; gene expression; genetic manipulation; laboratory mouse; lymphoma; molecular cloning; neoplasm /cancer genetics; neoplastic growth; nucleic acid sequence; oncogenes; pediatric neoplasm /cancer; radiation related neoplasm /cancer; tissue /cell culture; transforming growth factors; viral leukemogenesis; virus genetics

Lymphomagenesis is a mulitstep process in which the lymphoma cells become increasingly tumorigenic with time. In the initial phases of the disease, growth factor-dependent cells dominate; During the progression phases chromosome and oncogene rearrangements prevail. Leukemias possessing chromsomes or oncogene rearrangements have a poor prognosis compared to those lacking genetically-fixed rearrangements. Thus, it is of upmost importance to study the initial, growth-factor dependent phases of the disease so as to facilitate the design of rational approaches of intervention before gene rearrangementts occur. T leukemia/lymphomas of mice that are induced by radiation (an etiologic agent) initially comprise growth factor-dependent, autocrine cells. The nature of the growth factor (coined Lymphoma Growth Factor, LGF) and its cell surface receptor (LGF-R) will be studied by molecular cloning of genes encoding them. Molecular clones encoding the LGF and LGF-R will be studied on the nucleic acid and protein level. Antibodies specific for the LGF and LGF-R will be prepared. The site(s) at which LGF/LGF-R-positive cells first evolve in treated mice, as well as the characteristics of such cells will be studied. The existance and phenotypes of LGF/LGF-R-positive cells in non-treated mice will also be studied. Childhood Acute Lymphoblastic Leukemia of T cells (T-ALL) also appears to involve an LGF-dependent phase in which a growth factor similar to the murine LGF is implicated. Thus the study of the early, growth factor-dependent phase of murine lymphoma should further our understanding of childhood T-ALL as well.

淋巴瘤的发生是一个多步骤的过程， 随着时间的推移，细胞的致瘤性越来越强。 在初始 在疾病的各个阶段，生长因子依赖性细胞占主导地位; 在进展阶段，染色体和癌基因 重新安排占上风。 具有染色体的白血病或 癌基因重排的预后较差， 那些缺乏基因固定重排的人。 因此， 最重要的是研究初始的，生长因子依赖的 疾病的阶段，以便于设计合理的 在基因突变发生前进行干预的方法。 由辐射诱导的小鼠T白血病/淋巴瘤（一种 病原体）最初包括生长因子依赖性， 自分泌细胞 生长因子的性质（ 淋巴瘤生长因子及其细胞表面受体 （LGF-R）将通过编码LGF-R的基因的分子克隆来研究。 他们 编码LGF和LGF-R的分子克隆将在 从核酸和蛋白质水平进行研究。 特异性的抗体 将为LGF和LGF-R准备。 发生以下情况的地点 LGF/LGF-R阳性细胞首先在治疗的小鼠中进化， 将研究这种电池的特性。 的存在性 未处理小鼠中LGF/LGF-R阳性细胞的表型 也将被研究。 儿童T细胞急性淋巴细胞白血病（T-ALL）也 似乎涉及一个生长依赖性阶段， 与鼠LGF相似的因子也有牵连。 因此，研究 小鼠淋巴瘤早期生长因子依赖期 也会进一步加深我们对儿童T-ALL的理解。