Genomic alterations are known to be important determinants of leukemia development and response to treatment, but the full range of genetic alterations in childhood and adult ALL remains to be defined. In project 1, our overall aim is to identify and integrate the inherited and somatically acquired genomic variation associated with ALL treatment response. We will perform comprehensive genomic interrogation of pediatric and adult patients enrolled on clinical trials using common phenotypic endpoints (minimal residual disease, relapse) after defined chemotherapy on front-line ALL trials. Integrated bioinformatic analyses of ALL cell and host genomic data (arrays, sequencing, expression, epigenetics) will be used to prioritize genomic variation associated with poor response, identify pathways to provide potential new therapeutic avenues, and identify differences that may explain worse response in adults compared to children. |