Molecular Studies of Human All

人类的分子研究

• 批准号: 6515197
• 负责人: LINDA M BOXER
• 金额: $ 22.32万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-16 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6515197
• 关键词: acute lymphocytic leukemia; asparaginase; chromosome translocation; clinical research; human subject; microarray technology; neoplasm /cancer chemotherapy; neoplasm /cancer genetics; neoplasm /cancer relapse /recurrence; pediatric neoplasm /cancer; prednisolone; prognosis

DESCRIPTION (provided by applicant): Molecular cytogenetic studies have provided new information for the determination of prognosis in pediatric ALL. The genes involved in the major chromosomal translocations have been identified, and a number of studies have characterized the resulting fusion proteins. It is not known how the fusion proteins contribute to the process of leukemogenesis, however. Although knowledge of the different translocations in ALL is useful for predicting response to treatment, heterogeneity of response exists within the cytogenetic subgroups of ALL. We hypothesize that gene expression analysis will be able to distinguish among the different cytogenetic subgroups of pediatric B cell ALL. In addition, we will determine whether subgroups can be identified within several of the translocation groups of ALL and whether further information on prognosis can be obtained. We will examine whether a "relapse signature" can be identified by gene expression analysis of relapsed ALL samples within a translocation subtype. Evidence suggests that in vitro drug sensitivity correlates with in vivo response to the drug as measured by event-free survival. Microarray analysis will be used to follow changes in gene expression in response to a chemotherapeutic agent in both sensitive and resistant ALL cells. Further studies will be designed to identify genes that are directly correlated with expression of the fusion gene and important in the process of leukemogenesis. 1. Analysis and comparison of the gene expression profiles in pediatric ALL samples with t(9;22), t(1;19), t(4;ll), t(11;19), and t(12;21). 2. Correlation of gene expression patterns within the t(1;19) and t(12;21) ALL groups with prognosis and with relapse. 3. Determination of changes in gene expression in ALL cells, both sensitive and resistant, in response to chemotherapeutic agents. 4. Identification of fusion protein-specific events and studies of important genes and pathways in cell line

描述（由申请人提供）：分子细胞遗传学研究 提供了确定小儿预后的新信息。 主要染色体易位的基因已经 确定的，许多研究表征了由此产生的融合 蛋白质。融合蛋白如何有助于 但是，白血病发生。尽管了解不同的易位 一切对于预测对治疗的反应，反应的异质性很有用 存在于所有人的细胞遗传学亚组中。我们假设该基因 表达分析将能够区分不同的细胞遗传学 小儿B细胞的亚组。此外，我们将确定是否 可以在所有的几个易位组中识别亚组 以及是否可以获得有关预后的进一步信息。我们将检查 是否可以通过基因表达分析来识别“复发特征” 复发在易位亚型中的所有样品。有证据表明 体外药物敏感性与测量的体内反应相关 通过无事件的生存。微阵列分析将用于遵循更改 基因表达响应于敏感和敏感的化学治疗剂 抵抗所有细胞。进一步的研究将旨在确定基因 与融合基因的表达直接相关，在 白血病的过程。 1。小儿基因表达谱的分析和比较 t（9; 22），t（1; 19），t（4; ll），t（11; 19）和t（12; 21）的样品。 2。相关 t（1; 19）和t（12; 21）中的基因表达模式 预后和复发。 3。确定基因表达的变化 所有敏感和抗性的细胞都响应化学治疗性 代理商。 4。鉴定融合蛋白特异性事件和研究 细胞系中的重要基因和途径