The long-term goal of the Genomics of Acute Myeloid Leukemia Program Project Grant (GAML PPG) is to define all of the genetic events that contribute to the pathogenesis of AML, and to use this information to improve the risk assessment and treatment of patients with this disease. This goal will be addressed in a highly integrated and productive PPG structure that involves four projects and four cores. During the past 5 years, the members of this PPG developed the approaches (that are now widely used) to perform whole genome sequencing of AML genomes, and to validate all variants with custom capture arrays and deep digital sequencing. We have contributed 200 AML samples to The Cancer Genome Atlas for their AML project, which is led by two of our PPG members (Ley and Wilson). Although analysis of this enormous dataset is ongoing, these studies have led to the discovery of more than 200 recurrently mutated genes in AML, including DNMT3A, U2AF1, and IDH1, representing new classes of mutations that were not previously ( Acute myeloid leukemia is a heterogeneous group of malignancies of blood forming cells that are associated with a high rate of relapse and death, even with state-of-the-art therapy. The genetic basis of the disease must be solved so that risk assessment can be improved, and novel therapeutic approaches can be developed. We are sequencing the genomes and transcriptomes of AML cases to define the genetic factors that contribute to drug resistance and early relapse, which may provide new approaches for therapy.Public Health Relevance
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