Molecular Studies of Human All

人类的分子研究

• 批准号: 6604226
• 负责人: LINDA M BOXER
• 金额: $ 22.51万
• 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 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6604226
• 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已 为确定儿科 ALL 的预后提供了新信息。 与主要染色体易位有关的基因 已确定，并且许多研究已经描述了由此产生的融合 蛋白质。目前尚不清楚融合蛋白如何促进这一过程 然而，白血病发生。尽管对不同易位的了解 ALL 可用于预测治疗反应、反应异质性 存在于 ALL 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 儿童 B 细胞 ALL 亚组。此外，我们将确定是否 可以在 ALL 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” 易位亚型内的所有样本均复发。有证据表明，在 体外药物敏感性与测量的体内药物反应相关 通过无事件生存。微阵列分析将用于跟踪变化 敏感和化疗药物反应中的基因表达 耐药所有细胞。进一步的研究将旨在识别基因 与融合基因的表达直接相关，并且在 白血病发生的过程。 1. 儿童ALL基因表达谱分析比较 t(9;22)、t(1;19)、t(4;11)、t(11;19) 和 t(12;21) 的样本。 2. 相关性 t(1;19) 和 t(12;21) ALL 组内的基因表达模式 预后和复发情况。 3. 基因表达变化的测定 所有细胞，无论是敏感的还是耐药的，对化疗的反应 代理。 4. 融合蛋白特异性事件的鉴定和研究 细胞系中的重要基因和途径