IDH1 is an enzyme localized to the cytoplasm and peroxisomes and involved in citrate metabolism. Mutations at Arg132 of IDH1 are typically heterozygous mutations and considered gain of function mutations that lead to increased levels of 2-hydroxyglutarate which are believed to alter epigenetic regulation (ie, DNA methylation) in AML. Mutations of IDH1 appear to be mutually exclusive of mutations in TET2, another gene involved in regulation of DNA methylation, and also exclusive of mutations in IDH2. Mutations of IDH1 have been shown to lead to increased DNA methylation in AML. Recurrent missense mutation of Arg 132 in IDH1 has been reported in approximately 5-15% of cases of acute myeloid leukemia and is often associated with a normal karyotype, wild type CEBPA, wild type FLT3 and the presence of NPM1 mutations. In addition, this mutation has been reported in approximately 10-20% of cases with leukemic transformation of myeloproliferative neoplasms and has been reported in less than 5% of chronic phase primary myelofibrosis, less than 5% of myelodysplastic syndrome and rare cases of polycythemia vera, essential thrombocytosis and chronic myelomonocytic leukemia. The prognostic impact of IDH1 mutations in AML appears uncertain, however, in the settings of primary myelofibrosis and polycythemia vera, the presence of IDH1 mutation is independently associated with inferior survival. Mutant IDH1 represents a therapeutic target in some clinical settings.