ABL ONCOGENE AND MURINE AND HUMAN LEUKEMIAS

描述：(改编自调查人员的摘要)新方法 明确细胞癌基因使用的异常信号转导途径 在癌症的产生中是需要的。这笔赠款将提炼和 实施初级遗传筛查以识别细胞成分 Bcr-abl癌基因在白血病发生中的关键作用 患有费城染色体阳性的人类白血病。放映 救助方式是基于一系列部分丧失功能的救助 Bcr-abl基因突变，其酪氨酸激酶活性较高，但基因缺陷 成纤维细胞和造血细胞转化试验。基因能够 在转移后选择了一个强势琼脂生长表型 逆转录病毒载体中的cDNA文库克隆到bcr-abl突变体中 包含单元格。屏幕的基本概念已经演示给 工作，几个新基因正在研究中。这种类型的 对相互作用产生转化状态的基因进行无偏筛选 哺乳动物细胞应该为白血病的发病机制提供见解 和其他癌症。

DESCRIPTION: (adapted from the investigator's abstract) New approaches to define the abnormal signal transduction pathways used by cellular oncogenes in the generation of cancer are needed. This grant will refine and implement a primary genetic screen to identify the cellular components critical for the creation of leukemias by the Bcr-Abl oncogene associated with Philadelphia chromosome positive human leukemias. The screening approach is based on the rescue of a series of partial loss of function mutants of Bcr-Abl, which are tyrosine kinase active but defective in fibroblast and hematopoietic transformation assays. Genes capable of rescuing a strong agar growth phenotype are selected following transfer of cDNA libraries cloned in retroviral vectors into the Bcr-Abl mutant containing cells. The basic concept of the screen has been demonstrated to work, and several novel genes are under investigation. This type of unbiased screen for genes which interact to create the transformed state in mammalian cells should provide insights about the pathogenesis of leukemia and other cancers.