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MOLECULAR BIOLOGY OF B-CELL CHRONIC LYMPHOCYTIC LEUKEMIA

B 细胞慢性淋巴细胞白血病的分子生物学

基本信息

批准号：
2095402
负责人：
ELIZABETH W. NEWCOMB
金额：
$ 16万
依托单位：
NEW YORK UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1991
资助国家：
美国
起止时间：
1991-07-01 至 1995-06-30
项目状态：
已结题

项目摘要

Preliminary studies show transforming activity is associated with DNA from 6 cases of the advanced B cell malignancy, B cell chronic lymphocytic leukemia (B-CLL). The technique of DNA-mediated-gene-transfer was used to introduce high molecular weight DNA from B-CLL cells into mouse NIH 3T3 cells were inoculated into nude mice. Tumor formation is correlated with the transfer of DNA sequences which contain transforming activity. In this proposal we will clone the transforming gene(s) associated with advanced stages of B-CLL disease. The nude mouse tumorigenicity assay will monitor the cloning of the biologically active DNA fragment consisting of single copy human DNA will be used in Southern blot analysis to determine the pattern of gene arrangement in normal and malignant human lymphoid tissue. Northern blot analysis will determine expression of the gene(s) in mRNAs obtained from normal and malignant lymphoid tissues. To be cloned and its DNA sequence compared with the activated oncogene. The transforming DNA sequences will be analyzed by Southern blot using the active subclone to determine whether the genes are the same or different from one another. If the genes are the same, then fine restriction endonuclease mapping and DNA sequencing of the genes will determine the chromosomal change(s) involved in activation of the oncogene. The frequency of oncogene activation will be analyzed in B-CLL cases representative of different disease stages. This study will identify the transforming activity associated with B-CLL disease. Understanding the genetic mechanism of oncogene activation in B- CLL disease may have potential for improved patient diagnosis and treatment.

初步研究表明，转化活性与来自 6例晚期B细胞恶性肿瘤、B细胞慢性淋巴细胞白血病(B-CLL)。利用DNA介导的基因转移技术将B-CLL细胞的高分子量DNA导入小鼠NIH3T3 将细胞接种到裸鼠体内。肿瘤的形成与含有转化活性的DNA序列的转移。在这建议克隆晚期肺癌相关转化基因(S) B-CLL病分期。裸鼠致瘤性试验将监测具有生物活性的单链DNA片段的克隆复制的人类DNA将用于Southern印迹分析，以确定人类正常和恶性淋巴组织中的基因排列模式。 Northern印迹分析将确定S基因在mRNAs中的表达取自正常和恶性淋巴组织。将被克隆和它的将DNA序列与激活的癌基因进行比较。正在转化的DNA 序列将通过Southern杂交使用活性亚克隆进行分析确定这些基因是相同还是不同。如果这些基因是相同的，然后是精细的限制性内切酶图谱和DNA 基因测序将决定所涉及的染色体变化(S) 致癌基因的激活。癌基因激活的频率将在代表不同疾病阶段的B-CLL病例中进行分析。本研究将确定与B-CLL相关的转化活动疾病。了解B细胞癌基因激活的遗传机制慢性淋巴细胞性白血病可能会改善患者的诊断和治疗。