Pathogenesis and Therapy of IDH-TET-Mutant Myeloid Malignancies

Ross L. Levine, MD
Most recently, a series of candidate-gene and whole-genome studies has identified recurrent somatic mutations in AML patients, including TET2, ASXL1, DNMT3A, and EZH2 mutations. Of biological importance, the TET family of proteins has been shown to place a hydroxyl mark on methylated DNA and lead to DNA demethylation. We and others have found that TET2 mutations and IDH1 and IDH2 mutations lead to loss of DNA hydroxymethylation and hypermethylation phenotypes in leukemia patients.