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

2012; Lippincott Williams & Wilkins; Volume: 30; Issue: 12 Linguagem: Inglês

10.1200/jco.2011.39.2886

1527-7755

Verena I. Gaidzik, Peter Paschka, Daniela Späth, Marianne Habdank, Claus‐Henning Köhne, Ulrich Germing, Marie von Lilienfeld‐Toal, Gerhard Held, Heinz‐August Horst, Detlef Haase, Martin Bentz, Katharina S. Götze, Hartmut Döhner, Richard F. Schlenk, Lars Bullinger, Konstanze Döhner,

Epigenetics and DNA Methylation

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 < .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.