Acute myeloid leukemia (AML) results from genetic defects. Recurrent variations in chromosomal structures are common in AML, and several genes have been identified to be recurrently mutated in AML. Identification of these genetic defects in AML patients has improved diagnosis and treatment. However, more than twenty-five percent of AML patients carry no mutations in the known leukemia-associated genes, and the heterogeneity of AML and various survival outcomes suggest that as yet, undiscovered genes and pathways contribute to AML.
Dr. Gerben Duns performed high-throughput RNA sequencing and resequenced whole exomes, a portion of the genome, on 92 AML clinical samples to discover novel genes involved in AML. Mutations were identified within a gene called SETD2 in 7.6 percent of samples, suggesting a role for SETD2 in a subset of AML samples. The nature of the identified mutations suggests that these mutations are inactivating, which is in concordance with the recent identification of inactivating SETD2 mutations in several other cancer types.
Through in vitro and in vivo studies, Dr. Duns will examine the effects of the inactivating and mutating gene SETD2 as it contributes to AML development. Bioinformatic approaches are also used to investigate the potential association between the presence of SETD2 mutations and the response to therapy and disease outcome.
This study will provide insights into the mechanisms of AML pathogenesis, and will potentially reveal novel diagnostic and prognostic markers, as well as therapeutical targets.