Idh2, isocitrate dehydrogenase 2, is an enzyme located in the mitochondria. It catalyzes the oxidative decarboxylation of isocitrate to α -ketoglutarate, playing a crucial role in the tricarboxylic acid (TCA) cycle, which is essential for cellular energy production and metabolism [4,5,6].

Mutations in IDH2 are associated with several malignancies. In gliomas, tumors without IDH1 mutations often have IDH2 mutations affecting amino acid R172, and patients with such mutations have distinctive genetic and clinical characteristics and a better outcome [1]. In acute myeloid leukemia (AML), IDH2 mutations are common, occurring in 20-30% of cases. These mutations lead to DNA hypermethylation, aberrant gene expression, cell proliferation, and abnormal differentiation [3]. In urothelial cancer, gain-of-function of IDH2 induces reductive glutamine metabolism to stabilize Hif-1α expression, promoting metabolic reprogramming and chemoresistance [2].

In conclusion, IDH2 is vital for normal cellular metabolism. Its mutations are significantly associated with gliomas, AML, and urothelial cancer, among others. Research on IDH2-mutated models helps in understanding the disease mechanisms and developing targeted therapies, such as enasidenib for IDH2-mutated AML [5].