Landscape of TET2 mutations in acute myeloid leukemia View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2012-05

AUTHORS

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

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 × 10(9)/l, P=0.023), lower platelet count (mean 68.6 vs 92.4 × 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. More... »

PAGES

934

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/leu.2011.326

DOI

http://dx.doi.org/10.1038/leu.2011.326

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1006336284

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/22116554


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