<i>TET2</i> Mutations in Acute Myeloid Leukemia (AML): Results From a Comprehensive Genetic and Clinical Analysis of the AML Study Group

Abstract

Purpose The tet oncogene family member 2 (TET2) gene was recently identified to be mutated in myeloid disorders including acute myeloid leukemia (AML). To date, there is increasing evidence for a functional role of TET2 mutations (TET2 mut ) in AML. Thus, we explored the frequency, gene-expression pattern, and clinical impact of TET2 mut in a large cohort of patients with AML in the context of other AML-associated aberrations. Patients and Methods Samples from 783 younger adult patients with AML were analyzed for the presence of TET2 mut (coding exons 3 to 11), and results were correlated with data from molecular genetic analyses, gene-expression profiling, and clinical outcome. Results In total, 66 TET2 mut were found in 60 patients (60 of 783 patients; 7.6%), including missense (n = 37), frameshift (n = 16), and nonsense (n = 13) mutations, which, with one exception, were all heterozygous. TET2 mut were not correlated with distinct clinical features or genetic alterations, except for isocitrate dehydrogenase mutations (IDH mut ) that were almost mutually exclusive with TET2 mut (P &lt; .001). TET2 mut were characterized by only a weak gene-expression pattern, which, nevertheless, reflected TET2 mut -associated biology. TET2 mut did not impact the response to induction therapy and clinical outcome; the combination of patients who exhibited TET2 mut and/or IDH mut revealed shorter overall survival (P = .03), although this association was not independent from known risk factors. Conclusion TET2 mut were identified in 7.6% of younger adult patients with AML and did not impact the response to therapy and survival. Mutations were mutually exclusive with IDH mut , which supported recent data on a common mechanism of action that might obscure the impact of TET2 mut if compared against all other patients with AML.