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TET2 gene mutation is unfavorable prognostic factor in cytogenetically normal acute myeloid leukemia patients with NPM1+ and FLT3-ITD− mutations

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Abstract

Cytogenetically normal acute myeloid leukemia (cn-AML) is a group of heterogeneous diseases. Gene mutations are increasingly used to assess the prognosis of cn-AML patients and guide risk-adapted treatment. In the present study, we analyzed the molecular genetics characteristics of 373 adult cn-AML patients and explored the relationship between TET2 gene mutations or different genetic mutation patterns and prognosis. We found that 16.1 % of patients had TET2 mutations, 31.6 % had FLT3 internal tandem duplications (ITDs), 6.2 % had FLT3 tyrosine kinase domain mutations, 2.4 % had c-KIT mutations, 37.8 % had NPM1 mutations, 11.3 % had WT1 mutations, 5.9 % had RUNX1 mutations, 11.5 % had ASXL1 mutations, 3.8 % had MLL-PTDs, 7.8 % had IDH1 mutations, 7.8 % had NRAS mutations, 12.3 % had IDH2 mutations, 1.6 % had EZH2 mutations, and 14.7 % had DNMT3A mutations, while none had CBL mutations. Gene mutations were detected in 76.94 % (287/373) of all patients. In the NPM1m+ patients, those with TET2 mutations were associated with a shorter median overall survival (OS) as compared to TET2 wild-type (wt) patients (9.9 vs. 27.0 months, respectively; P = 0.023); Interestingly, the TET2 mutation was identified as an unfavorable prognostic factor and was closely associated with a shorter median OS as compared to TET2-wt (9.5 vs. 32.2 months, respectively; P = 0.013) in the NPM1m+/FLT3-ITDm− patient group. Thus, identification of TET2 combined with classic NPM1 and FLT3-ITD mutations allowed us to stratify cn-AML into distinct subtypes.

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Acknowledgments

This work was supported in part by grants from National Key Scientific Projects of China (2011CB933501); the National Natural Science Foundation of China (81270617,81302046); Jiangsu Province Natural Science Fund for Distinguished Young Scholars; Foundation of Jiangsu Province Health Department (H200915); and Specialized Research Fund for the Doctoral Program of Higher Education of China (20133201120021).

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The authors have no conflicts of interest to disclose.

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Authors and Affiliations

  1. Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, Jiangsu province, People’s Republic of China

    Xiaopeng Tian, Yang Xu, Jia Yin, Hong Tian, Suning Chen, Depei Wu & Aining Sun

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  1. Xiaopeng Tian
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  2. Yang Xu
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  3. Jia Yin
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  4. Hong Tian
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  5. Suning Chen
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  6. Depei Wu
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  7. Aining Sun
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Correspondence to Depei Wu or Aining Sun.

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X. Tian and Y. Xu contributed equally to this work.

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Tian, X., Xu, Y., Yin, J. et al. TET2 gene mutation is unfavorable prognostic factor in cytogenetically normal acute myeloid leukemia patients with NPM1+ and FLT3-ITD− mutations. Int J Hematol 100, 96–104 (2014). https://doi.org/10.1007/s12185-014-1595-x

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