Landscape of TET2 mutations in acute myeloid leukemia

被引:190
作者
Weissmann, S. [1 ]
Alpermann, T. [1 ]
Grossmann, V. [1 ]
Kowarsch, A. [1 ]
Nadarajah, N. [1 ]
Eder, C. [1 ]
Dicker, F. [1 ]
Fasan, A. [1 ]
Haferlach, C. [1 ]
Haferlach, T. [1 ]
Kern, W. [1 ]
Schnittger, S. [1 ]
Kohlmann, A. [1 ]
机构
[1] MLL Munich Leukemia Lab, D-81377 Munich, Germany
关键词
TET2; mutations; next-generation sequencing; acute myeloid leukemia; prognosis; GENE; DIAGNOSIS; RECOMMENDATIONS; PROGNOSIS; SECONDARY; PCR; AML;
D O I
10.1038/leu.2011.326
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 x 10(9)/l, P = 0.023), lower platelet count (mean 68.6 vs 92.4 x 10(9)/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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收藏
页码:934 / 942
页数:9
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