ABL ONCOGENE AND MURINE AND HUMAN LEUKEMIAS

描述：（改编自研究者摘要） 确定细胞癌基因使用的异常信号转导途径 是需要的。 这笔赠款将完善和 进行初步遗传筛查，以确定细胞成分 Bcr-Abl癌基因相关的白血病形成的关键 费城染色体阳性的人类白血病患者 筛选 方法是基于一系列部分功能丧失的抢救 Bcr-Abl的突变体，具有酪氨酸激酶活性，但在 成纤维细胞和造血转化测定。 基因能够 在转移以下细胞后选择拯救强琼脂生长表型的细胞： 将逆转录病毒载体中的cDNA文库克隆到Bcr-Abl突变体中 包含细胞。 屏幕的基本概念已被证明， 工作，几个新的基因正在研究中。 这种类型的 无偏见的筛选基因的相互作用，创造转化状态， 哺乳动物细胞应该提供关于白血病发病机制的见解 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.