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Acute Leukemias

Landscape of TET2 mutations in acute myeloid leukemia

Leukemia volume 26, pages 934–942 (2012)Cite this article

Abstract

We investigated ten–eleven translocation 2 (TET2) mutations in acute myeloid leukemia (AML), their correlation with other gene mutations and prognostic value. By deep-sequencing, 131 somatic TET2 mutations were identified in 87/318 (27.4%) patients. Of 87 mutated cases, 44 (50.6%) carried two mutations. TET2 mutations were concomitantly observed with mutations in NPM1, FLT3-ITD, FLT3-TKD, JAK2, RUNX1, CEBPA, CBL and KRAS. However, TET2 mutations rarely concomitantly occurred with IDH1mut or IDH2mut (2/251 or 0/184; P=0.046 and P=0.003, respectively). TET2 mutations were associated with normal karyotype AML (CN-AML) (62/206 (30.1%) CN-AML vs 20/107 (18.7%) aberrant karyotype; P=0.031), higher white blood cell count (mean 65.3 vs 40.3 × 109/l, P=0.023), lower platelet count (mean 68.6 vs 92.4 × 109/l, P=0.03) and higher age (67.5 vs 65.2 years, P<0.001). Survival analyses were restricted to de novo CN-AML patients (n=165) and showed inferior event-free survival (EFS) of TET2 mutations compared with TET2wt (median: 6.7 vs 18.7 months, P=0.009). This negative effect of TET2 mutation on EFS was particularly observed in patients ⩽65 years (median: 8.9 months vs not reached (n.r.), P=0.027) as well as in patients of the European LeukemiaNet favorable-risk subgroup, that is, patients harboring mutated CEBPA and/or mutated NPM1 without FLT3-ITD (median: 10.3 vs 41.3 months, P=0.048). These data support a role for TET2 as an important prognostic biomarker in AML.

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Authors and Affiliations

  1. MLL Munich Leukemia Laboratory, Munich, Germany

    S Weissmann, T Alpermann, V Grossmann, A Kowarsch, N Nadarajah, C Eder, F Dicker, A Fasan, C Haferlach, T Haferlach, W Kern, S Schnittger & A Kohlmann

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Correspondence to A Kohlmann.

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Competing interests

CH, TH, WK, and SS are part-owners of the MLL Munich Leukemia Laboratory GmbH. SW, TA, VG, AnKo, NN, CE, FD, AF and AlKo are employed by MLL Munich Leukemia Laboratory.

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SW, AlKo and SS designed the study. SW, VG, CE, FD and AF performed research and generated data. SW, TA, AnKo, NN and AlKo analyzed and interpreted the data. SW wrote the paper.

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Weissmann, S., Alpermann, T., Grossmann, V. et al. Landscape of TET2 mutations in acute myeloid leukemia. Leukemia 26, 934–942 (2012). https://doi.org/10.1038/leu.2011.326

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