Acute myeloid leukemia (AML) is one of the deadliest blood cancers. Current treatments are very toxic and most patients will die from their disease. Metabolism is the process that converts food into energy and building blocks for making and maintaining our tissues. Metabolism is also essential for cancer cells and we have known for over a hundred years that cancer cells have different metabolism requirements than normal cells. The challenge has been to fully understand these differences and to target these unique requirements to kill cancer cells without killing normal cells. The DeGregori lab has generated exciting data showing that a new therapy for AML (“FLT3-inhibitor”) results in dramatic changes in metabolism within leukemia cells. FLT3 has been shown to be important for the formation and growth of AML. The new FLT3-inhibitor therapy is being tested in hospitals for patients with AML. However, while a lot of AML cells die after treatment with FLT3-inhibitor, enough leukemia cells survive to rapidly cause the AML to come back. Proposed studies will attempt to take advantage of the new weaknesses of AML cells caused by this therapy, in order to develop new combination therapies that better eliminate leukemia cells with reduced side-effects to the patients. These new therapies will be like “one-two punches”, with the first punch (FLT3-inhibitor) weakening the AML cells. The second punch takes advantage of this weakness, helping to eliminate the surviving AML cells. The development of these new combination treatments is expected to lead to better results for patients with AML, using less toxic drugs.