Missy’s Story: Connecting Krebs Cycle to Acute Myeloid Leukemia Treatment

Missy’s Story: Connecting Krebs Cycle to Acute Myeloid Leukemia Treatment Abstract: This case examines the medical journey of a colleague in our community, Dr. Melissa Dore (Missy), a woman in her 50s who was diagnosed with Acute Myeloid Leukemia (AML) a few months before this molecular case was proposed and developed based on her experience. This case starts with watching the interview with Missy regarding her symptoms, treatment journey and the identification of her mutation in an important enzyme of the Krebs Cycle (isocitrate dehydrogenase 2) as well as the drug that targets and inhibits the dysfunctional enzyme. This case examines how that enzyme and drug function as one of Missy’s treatments for AML. Molecules explored: The primary molecule studied in this case is Isocitrate dehydrogenase 2. A mutant version of the enzyme facilitates the abnormal conversion of alpha-ketoglutarate (α-KG) to 2-hydroxyglutarate (2-HG) and can lead to AML. Here we also explore how a drug (enasidenib) binds to the mutant enzyme, prevents its activity, and helps treat AML.