Abstract 1369 Modeling Isocitrate Dehydrogenase 2 Mutations in Acute Myeloid Leukemia: Exploring how the drug AG-221 Inhibits 2-hydroxyglutarate Production and Restores Blood Cell Differentiation

Acute myeloid leukemia (AML) is a cancer that affects the blood and bone marrow, specifically through improper differentiation of young blood cells into healthy red blood cells, white blood cells, and platelets. Some of the mutations involved in AML have been traced back to the Isocitrate Dehydrogenase 2 (IDH2) enzyme. IDH2 is an enzyme within the citric acid cycle that converts isocitrate to α-ketoglutarate (α-KG) with NADP+ being reduced to NADPH as an important cofactor. Mutations in IDH2, such as R140Q and R172K, cause the protein to convert α-KG to the oncometabolite 2-hydroxyglutarate (2HG).