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Each year, approximately 1,000 Americans aged 20 years or younger are diagnosed with acute myeloid leukemia (AML). Currently, no drugs can eradicate all AML cells in pediatric patients, and cells remaining after treatment often cause disease recurrence and poor survival. Dr. Li and colleagues have found that two mitochondrial enzymes that function in energy metabolism, known as DHODH or SDH, shield leukemia cells from eradication by immune cells. Dr. Li will use models relevant to pediatric AML to ask how these factors block anti-cancer immune responses and test effectiveness of a first-in-class leukemia cell-specific DHODH inhibitor combined with existing immune therapy in eradicating AML. If successful, this study will lead to development of new anti-leukemia drugs that could approach a cure for childhood AML.