Molecular Studies of Human All

描述(申请人提供)：分子细胞遗传学研究 为判断儿童ALL的预后提供了新的信息。 参与主要染色体易位的基因是 已经确定，许多研究已经表征了由此产生的融合 蛋白质。目前尚不清楚这些融合蛋白是如何作用于 然而，白血病的发生。尽管对人类不同易位的了解 ALL有助于预测治疗反应、反应的异质性 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 儿童B细胞ALL亚群。此外，我们将确定是否 可以在ALL的几个易位组中识别出亚组 以及能否获得进一步的预后信息。我们将研究 是否可以通过基因表达分析来识别“复发特征” 复发了一个易位亚型内的所有样本。有证据表明， 体外药物敏感性与体内对药物的反应相关 通过无事故生存。将使用微阵列分析来跟踪 对化疗药物敏感和敏感的患者的基因表达 抵抗所有细胞。进一步的研究将被设计用来识别 与融合基因的表达直接相关，并在 白血病的发生过程。 1.儿童急性淋巴细胞白血病基因表达谱的分析比较 T(9；22)、t(1；19)、t(4；11)、t(11；19)和t(12；21)的样本。2.关联性 T(1；19)和t(12；21)组内的基因表达模式 预后和复发。3.基因表达变化的测定 所有细胞，包括敏感细胞和耐药细胞，对化疗的反应 探员们。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

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