Landscape of TET2 mutations in acute myeloid leukemia

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.