Grants - V Scholar Grants - Maine - 2016

Jennifer Trowbridge, Ph.D.

Funded by the Hearst Foundation

Acute myeloid leukemia (AML) is an aggressive blood cancer where <30% of all patients are long-term survivors and >11,000 patients die per year in the United States alone. Treatment of AML has changed little in the past two decades, and is ineffective in curing patients of their disease, as the majority will relapse within five years.

Doctors and scientists recently investigated the DNA of AML patients and found that many patients contain mutations in a gene called DNA methyltransferase 3A (DNMT3A). Strikingly, many healthy adults also have DNMT3A mutations in their blood cells. This suggests that additional mutations (not just DNMT3A alone) are required to develop AML. Currently, scientists and doctors have a poor understanding of why and how mutations in DNMT3A frequently, but not always, lead to the development of blood cancer. This is important to understand for two reasons. First, to develop new ways to assess risk of AML in healthy people with DNMT3A mutations. Second, to create new therapies that stop DNMT3A-mutant cells from causing AML to recur after treatment.

Our work focuses on the initial changes that drive cancer development or relapse. Therefore, we cannot directly use AML patients samples that already contain many mutations. I propose to use new mouse models precisely engineered to carry mutations found in human AML patients. My research will use these models to show why and how AML develops from mutations in DNMT3A.

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