VIRAL MALIGNANT LYMPHOMAGENESIS IN X-IRRADIATED MICE

X 射线照射小鼠中的病毒恶性淋巴瘤发生

• 批准号: 3171915
• 负责人: Martin nmi Haas
• 金额: $ 3.73万
• 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/3171915
• 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.

淋巴瘤发生是一个多步骤的过程，其中淋巴瘤 随着时间的推移，细胞的致瘤性越来越强。 在最初的 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。 具有染色体或 与癌基因重排相比，癌基因重排的预后较差 那些缺乏基因固定重排的人。 因此，它是 最重要的是研究最初的、生长因子依赖性的 疾病的各个阶段，以便于设计合理的治疗方案 基因重排发生之前的干预方法。 辐射诱发的小鼠 T 白血病/淋巴瘤（一种 病因）最初包括生长因子依赖性， 自分泌细胞。 生长因子（创造的 淋巴瘤生长因子（LGF）及其细胞表面受体 （LGF-R）将通过编码基因的分子克隆进行研究 他们。 编码LGF和LGF-R的分子克隆将是 在核酸和蛋白质水平上进行研究。 抗体特异性 将为LGF和LGF-R做好准备。 所在站点 LGF/LGF-R 阳性细胞首先在接受治疗的小鼠中进化，并且 将研究此类细胞的特征。 存在 以及未治疗小鼠中 LGF/LGF-R 阳性细胞的表型 也将被研究。 T 细胞儿童急性淋巴细胞白血病 (T-ALL) 也 似乎涉及 LGF 依赖阶段，其中生长 与小鼠 LGF 类似的因子也参与其中。 因此研究 鼠淋巴瘤的早期生长因子依赖性阶段 也应该进一步加深我们对儿童 T-ALL 的理解。

项目成果

Radiation leukemia virus and X-irradiation induce in C57BL/6 mice two distinct T-cell neoplasms: a growth factor-dependent lymphoma and a growth factor-independent lymphoma.

放射性白血病病毒和 X 射线照射在 C57BL/6 小鼠中诱导两种不同的 T 细胞肿瘤：生长因子依赖性淋巴瘤和生长因子非依赖性淋巴瘤。

• DOI: 10.1016/0145-2126(87)90046-4
• 发表时间: 1987
• 期刊: Leukemia research
• 影响因子: 2.7
• 作者: Haas,M;Altman,A;Rothenberg,E;Bogart,MH;Jones,OW
• 通讯作者: Jones,OW

Insulin-like growth factor-I supports proliferation of autocrine thymic lymphoma cells with a pre-T cell phenotype.

胰岛素样生长因子-I 支持具有前 T 细胞表型的自分泌胸腺淋巴瘤细胞的增殖。

• 发表时间: 1990
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Gjerset,RA;Yeargin,J;Volkman,SK;Vila,V;Arya,J;Haas,M
• 通讯作者: Haas,M

Mechanism of T-cell lymphomagenesis: transformation of growth-factor-dependent T-lymphoblastoma cells to growth-factor-independent T-lymphoma cells.

T细胞淋巴瘤发生机制：生长因子依赖性T淋巴细胞瘤细胞向生长因子非依赖性T淋巴瘤细胞的转化。

• DOI: 10.1073/pnas.81.6.1742
• 发表时间: 1984
• 期刊: Proceedings of the National Academy of Sciences of the United States of America
• 影响因子: 11.1
• 作者: Haas,M;Altman,A;Rothenberg,E;Bogart,MH;Jones,OW
• 通讯作者: Jones,OW

Autocrine growth and progression of murine X-ray-induced T cell lymphomas.

小鼠 X 射线诱导的 T 细胞淋巴瘤的自分泌生长和进展。

• DOI: 10.1002/j.1460-2075.1986.tb04426.x
• 发表时间: 1986
• 期刊: The EMBO journal
• 作者: Haas,M;Mally,MI;Bogenberger,JM;Bogart,MH;Buchanan,MA;Augery-Bourget,Y;Hyman,R;Vogt,M
• 通讯作者: Vogt,M

Immunopathology of B-cell lymphomas induced in C57BL/6 mice by dualtropic murine leukemia virus (MuLV).

双嗜性鼠白血病病毒 (MuLV) 在 C57BL/6 小鼠中诱导 B 细胞淋巴瘤的免疫病理学。

• 发表时间: 1982
• 期刊: The American journal of pathology
• 作者: Pattengale,PK;Taylor,CR;Twomey,P;Hill,S;Jonasson,J;Beardsley,T;Haas,M
• 通讯作者: Haas,M