Pharmacogenomics of childhood AML susceptibility and treatment response.

Although acute myeloid leukemia (AML) causes a substantial disease and treatment burden in both children and adults, the causes of AML and unsuccessful treatment are poorly understood. Currently, many scientists believe that naturally occurring genetic variation changes AML susceptibility and relapse risks. This application seeks to identify these specific genetic variations by searching throughout the genome with a genome-wide association study (GWAS). This research seeks to find these genetic changes with three specific aims. Aim 1 will use the Illumina 550 HH Bead Chip to perform genome-wide scans on 300 Caucasian patients treated on cooperative group AML protocols from the Children's Oncology Group (COG). These data will be compared with genome-wide scans already performed and available at no cost in 1200 Caucasian control patients at the Center for Applied Genomics (CAG) at The Children's Hospital of Philadelphia. Aim 2 will confirm the findings from the genome-wide scan from Aim 1 in an additional 2000 patients, of whom 1000 have been treated on COG trials and an additional 1000 controls from the (CAG). Aim 3 will compare the genome-wide scans of patients with AML who relapsed with the genome-wide scans of patients who did not relapse in order to identify genotypes associated with an increased risk of leukemia relapse.