Molecular Studies of Human All

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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