TET2 Mutations in Acute Myeloid Leukemia (AML): Results From a Comprehensive Genetic and Clinical Analysis of the AML Study Group
Open accessAbstract
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.
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Up to 90% of diffuse intrinsic pontine gliomas (DIPG) harbour a point mutation in canonical (HIST1H3B (H3.1)) or variant (H3F3A (H3.3)) histone H3, resulting in a lysine 27 to methionine (K27M) substitution.
“Of these, up to 90% of diffuse intrinsic pontine gliomas (DIPG) harbour a point mutation in canonical ( HIST1H3B (H3.1)) or variant ( H3F3A (H3.3)) histone H3, resulting in a lysine 27 to methionine (K27M) substitution 101-103 .”
From The roles of DNA, RNA and histone methylation in ageing and cancer (2019) · cites this paper as [102]
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- Authors
- Gaidzik, V. I., Paschka, P., Späth, D., Habdank, M., Köhne, C.-H., Germing, U., von Lilienfeld-Toal, M., Held, G., Horst, H.-A., Haase, D., Bentz, M., Götze, K., Döhner, H., Schlenk, R. F., Bullinger, L., & Döhner, K.
- Affiliations
- Universität Ulm (DE)
- Verena I. Gaidzik, Peter Paschka, Daniela Späth, Marianne Habdank, Hartmut Döhner, Richard F. Schlenk, Lars Bullinger, and Konstanze Döhner, Universitätsklinikum Ulm, Ulm; Claus-Henning Köhne, Klinikum Oldenburg, Oldenburg; Ulrich Germing, Universitätsklinikum Düsseldorf, Düsseldorf; Marie von Lilienfeld-Toal, Universitätsklinikum Bonn, Bonn; Gerhard Held, Universitätsklinikum des Saarlandes, Homburg; Heinz-August Horst, Universitätsklinikum Schleswig-Holstein, Kiel; Detlef Haase, Universitätsklinikum...
- Corresponding author
- Döhner, Hartmut
- Döhner, Konstanze
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2012-04-20
- Volume
- 30
- Issue
- 12
- Pages
- 1350-1357
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W4238020764
- Cited by
- 185
- References
- 37
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 7 · 2023: 14 · 2022: 6 · 2021: 12 · 2020: 13 · 2019: 11 · 2018: 9 · 2017: 16 · 2016: 16 · 2015: 26 · 2014: 21 · 2013: 17 · 2012: 9
- FWCI
- 15.45
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Oncology (publishedVersion)
- mediaTUM (Technical University of Munich) (submittedVersion)
- GRO (submittedVersion, cc-by)
- Funders
- Deutsche Forschungsgemeinschaft (BU 1339/3-1)
- Topics
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- TET2 mutation, acute myeloid leukemia, IDH mutation, mutation frequency, gene expression profiling, clinical outcomes, overall survival, induction therapy response, risk stratification
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