DNA methyltransferase 3A characterization in clonal hematopoiesis, aging and acute myeloid leukemia

The expected growth of the older adult population in the United States over the next several decades will have an unprecedented impact on the health care system. Research has shown that age is the greatest risk factor for developing cancer and certain hematological malignances. Insights on acute myeloid leukemia have suggested that premalignant somatic mutations in stem cells are responsible for age associated medical conditions. Persistence of preleukemic clones and the risk of relapse is linked with an abnormal DNA methyltransferase 3A (DNMT3A) gene especially in the R882H region which may lead to a phenomenon known as clonal hematopoiesis. The DNMT3A gene provides instructions for making an enzyme that establishes DNA methylation patterns and is believed to form the initial mutation in acute myeloid leukemia. Because of the significance of DNMT3A mutations in the pathogenesis of leukemias and clonal hematopoiesis with respect to the geriatric population, the goal of the thesis was to generate DNMT3A proteins for future research via a bacterial expression vector. Wildtype and dominant negative DNMT3A proteins were not successfully generated, but the study is still an ongoing process. The overview of the entire long term study is to focus on the mechanism insight on DNMT3A activity and its contribution to acute myeloid leukemia development