GCKR MEDIATED SIGNAL TRANSDUCTION AND LEUKEMIC TRANSFORM

GCKR 介导的信号转导和白血病转化

• 批准号: 2564624
• 负责人: JOSEPH M TUSCANO
• 金额: $ 7.4万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 2001-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2564624
• 关键词: animal genetic material tag; athymic mouse; biological signal transduction; chronic myelogenous leukemia; enzyme activity; gene induction /repression; genetically modified animals; human genetic material tag; human tissue; neoplasm /cancer genetics; neoplastic transformation; oncogenes; protein kinase; receptor; tissue /cell culture

DESCRIPTION (Applicant's Description): Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disorder of the primitive hematopoietic stem cell. CML accounts for approximately 25% of all adult leukemia. The BCR-ABL oncogene probably represents the initiating event in nearly all CML, although additional genetic events are required for the full malignant phenotype. The recently described serine-threonine kinases GCK and GCKR are known to activate the pathway that is thought to mediate the transforming ability of BCR-ABL. Specifically, based on work that is to be presented under Preliminary Studies, the applicants hypothesize that GCKR specifically associates with, and is activated by, BCR-ABL and is likely a critical element in BCR-ABL's transforming potential. Based on this they propose to: 1) examine the basic elements and requirements that mediate the association between GCKR and BCR-ABL; 2) examine the functional consequences of the BCR-ABL relationship with GCKR; 3) assess the in vivo transforming potential of GCK and GCKR. Elucidating the role of GCKR in BCR-ABL mediated transformation will allow for a better understanding of the mechanism of oncogenic transformation, and thus allow for the development of improved treatment and prognostication strategies for CML. The applicant's training in molecular biology, immunology, and clinical oncology, in addition to his direct experience with the initial cloning of GCKR put him in the unique position to pursue the studies proposed here.

描述（申请人的描述）： 慢性骨髓性白血病（CML）是一种克隆骨髓增生性疾病 原始造血干细胞的。 CML大约帐户 所有成人白血病的25％。 BCR-ABL癌基因可能代表 尽管其他遗传事件是 完全恶性表型所需。 最近描述的 已知丝氨酸 - 苏氨酸激酶GCK和GCKR激活该途径 被认为可以介导BCR-ABL的转化能力。 具体来说， 基于将在初步研究中介绍的工作 申请人假设GCKR专门与 被BCR-ABL激活，可能是BCR-ABL的关键要素 转变潜力。 基于此，他们建议：1）检查 介导GCKR之间关联的基本要素和要求 和bcr-abl; 2）检查BCR-ABL的功能后果 与GCKR的关系； 3）评估GCK的体内转化潜力 和GCKR。 阐明GCKR在BCR-ABL介导的转化中的作用 将可以更好地了解致癌机制 转型，从而允许开发改进的治疗和 CML的预后策略。 申请人的分子培训 生物学，免疫学和临床肿瘤学，除了他的直接 GCKR最初克隆的经验使他处于独特的位置 追求这里提出的研究。