Molecular Studies of Human All

描述（由申请人提供）：分子细胞遗传学研究 为确定儿童ALL的预后提供了新的信息。 参与主要染色体易位的基因已经被 确定，和一些研究的特点，所产生的融合 proteins.目前尚不清楚融合蛋白如何参与细胞的增殖过程。 然而，白血病发生。虽然对不同易位的了解， ALL可用于预测治疗反应、反应异质性 存在于ALL的细胞遗传学亚群中。我们假设这个基因 表达分析将能够区分不同的细胞遗传学 儿科B细胞ALL的亚组。此外，我们将确定是否 可以在ALL的几个易位组中鉴定出亚组 以及是否可以获得关于预后的进一步信息。我们将研究 是否可以通过基因表达分析鉴定“复发标记”， 易位亚型内的复发ALL样本。有证据表明，在 体外药物敏感性与体内对药物的反应相关 无事件生存。微阵列分析将用于跟踪 在敏感性和敏感性细胞中， 耐药ALL细胞进一步的研究将被设计来识别基因， 与融合基因的表达直接相关，并且在 白血病发生的过程 1.儿童急性淋巴细胞白血病基因表达谱的分析与比较 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组中的基因表达模式， 预后和复发。3.确定在小鼠中基因表达的变化 敏感和耐药的ALL细胞对化疗药物的反应 剂. 4.融合蛋白特异性事件的鉴定和融合蛋白的研究 细胞系中的重要基因和途径

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