MOLECULAR GENETICS OF HUMAN LEUKEMIAS AND LYMPHOMAS

人类白血病和淋巴瘤的分子遗传学

• 批准号: 3079598
• 负责人: TIMOTHY C. MEEKER
• 金额: $ 6.67万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-02-01 至 1989-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3079598
• 关键词: B lymphocyte; chromosome disorders; chromosome translocation; complementary DNA; genetic library; genetic manipulation; genetic mapping; genetic transcription; human tissue; lymphocytic leukemia; lymphoma; molecular cloning; monoclonal antibody; neoplasm /cancer genetics; nucleic acid sequence; oncogenes; synthetic antigens

It is clear that many B lymphocytic cancers are associated with characteristic chromosomal abnormalities. These chromosomal aberrations appear to result in disordered gene expression which may be fundamental to oncogenesis. The genes that are deregulated by chromosomal abnormalities and cause the malignant phenotype are called proto-oncogenes. This proposal will investigate the genetic alteration resulting from the translocation (14,18) that occurs in the majority of nodular lymphoma and the translocation(1,19) that occurs in approximately 30% of pre-B cell acute lymphocytic leukemia. We propose that two new oncogenes, bcl-2 and bcl-3, are located adjacent to these points of translocation. This proposal will focus on the cloning and characterization of these oncogenes. This project will begin with the cloning of the breakpoints noted above from genomic libraries and the identification of an adjacent transcribed gene by Northern blotting. These transcribed genes will then be cloned from cDNA libraries. The genomic and cDNA clones of these genes (bcl-2 and bcl-3) will then be characterized by restriction mapping, S1 mapping and sequencing. In an effort to understand the range of genetic alteration in these diseases, multiple tissue samples will be studied by Southern blotting, Northern blotting and perhaps at the sequence level. The cloned genes will be expressed in E. coli to isolate material to immunize for antibody production. Similarly, the derived amino acid sequence of the gene products will be used to make peptides to immunize animals for antibody production for initial protein studies. This investigation will result in an understanding of the genetic basis of human nodular lymphoma and pre-B cell acute lymphocytic leukemia. This investigation will lay the foundation for improved therapeutic and preventive strategies for these diseases.

很明显，许多B淋巴细胞癌与 典型的染色体异常 这些染色体畸变 似乎导致基因表达紊乱，这可能是根本的， 肿瘤发生 染色体异常导致基因失调 并导致恶性表型的基因称为原癌基因。 这 这项提案将调查由基因突变引起的基因改变。 易位（14，18），发生在大多数结节性淋巴瘤， 大约30%前B细胞发生易位（1，19 急性淋巴细胞白血病 我们提出两个新的癌基因bcl-2和 bcl-3位于这些易位点附近。 这 该提案将集中在克隆和表征这些 致癌基因 本项目将从克隆断点开始开始 从基因组文库和鉴定相邻的 通过北方印迹分析转录的基因。 这些转录的基因 从cDNA文库中克隆。 这些基因的基因组和cDNA克隆 然后将通过限制性酶切图谱表征（bcl-2和bcl-3）， 作图和测序。 为了了解基因的范围， 在这些疾病中，多个组织样本将被研究， Southern印迹，北方印迹，也许在序列水平。 克隆的基因将在E.分离材料， 免疫以产生抗体。 类似地，衍生的氨基酸 基因产物的序列将用于制备免疫肽， 用于抗体生产的动物，用于初步蛋白质研究。 这 研究将导致对人类遗传基础的理解 结节性淋巴瘤和前B细胞急性淋巴细胞白血病。 这 研究将为改善治疗和 这些疾病的预防策略。