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: 3079599
• 负责人: TIMOTHY C. MEEKER
• 金额: $ 6.59万
• 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/3079599
• 关键词: B lymphocyte; RNA; chromosome disorders; chromosome translocation; complementary DNA; electrophoresis; genetic library; genetic manipulation; genetic mapping; genetic transcription; human tissue; laboratory mouse; laboratory rabbit; lymphocytic leukemia; lymphoma; molecular cloning; monoclonal antibody; neoplasm /cancer genetics; nucleic acid hybridization; nucleic acid sequence; oncogenes; restriction mapping; substance P; 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淋巴细胞性癌症与 典型的染色体异常。这些染色体的异常 似乎会导致基因表达紊乱，这可能是 致癌作用。因染色体异常而失控的基因 并导致恶性表型被称为原癌基因。这 提案将调查由基因突变引起的基因变化 易位(14，18)，发生在大多数结节性淋巴瘤和 易位(1，19)发生在大约30%的前B细胞中 急性淋巴细胞性白血病。我们提出了两个新的癌基因bcl2和bcl2。 BCL-3位于这些易位点附近。这 提案的重点将是克隆和表征这些 致癌基因。这个项目将从克隆断点开始 以上从基因组文库中注意到的，并鉴定了邻近的 Northern blotting转录的基因。然后这些转录的基因就会 从cDNA文库中克隆得到。这些基因的基因组和cDNA克隆 (BCL-2和BCL-3)然后将通过限制图S1来表征 测绘和测序。为了了解基因的范围 在这些疾病中，多个组织样本将通过 Southern blotting、Northern blotting以及可能在序列水平上。 克隆的基因将在大肠杆菌中表达，以分离材料 免疫以产生抗体。同样，衍生的氨基酸 基因产物的序列将被用来制造多肽进行免疫 用于初步蛋白质研究的抗体生产的动物。这 调查将使我们了解人类的遗传基础 结节性淋巴瘤和前B细胞急性淋巴细胞白血病。这 调查将为改进治疗和治疗奠定基础 这些疾病的预防策略。