GCKR MEDIATED SIGNAL TRANSDUCTION AND LEUKEMIC TRANSFORM

GCKR 介导的信号转导和白血病转化

• 批准号: 2896405
• 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/2896405
• 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）： 慢性粒细胞白血病（CML）是一种克隆性骨髓增殖性疾病 原始造血干细胞。 CML 约占 占所有成人白血病的 25%。 BCR-ABL 癌基因可能代表 几乎所有 CML 的始发事件，尽管额外的遗传事件 完全恶性表型所需的。 最近描述的 丝氨酸-苏氨酸激酶 GCK 和 GCKR 已知可激活以下途径： 被认为介导 BCR-ABL 的转化能力。 具体来说， 基于初步研究中提出的工作， 申请人假设 GCKR 与特定相关，并且是 由 BCR-ABL 激活，并且可能是 BCR-ABL 中的关键元素 转化潜力。 基于此，他们建议：1）检查 协调 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 有助于更好地了解致癌机制 转变，从而允许开发改进的治疗方法和 CML 的预测策略。 申请人的分子培训 除了他的直接研究之外，生物学、免疫学和临床肿瘤学 最初克隆 GCKR 的经验使他处于独特的地位 继续进行这里提出的研究。