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Ethnic variation of TET2 SNP rs2454206 and association with clinical outcome in childhood AML: a report from the Children’s Oncology Group

Leukemia volume 29, pages 2424–2426 (2015)Cite this article

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Epigenetic deregulation is a common finding in myeloid malignancies, and epigenetic therapies have been used successfully to treat patients with acute myeloid leukemia (AML) and myelodysplastic syndrome. Inactivating mutations of TET2 have been found in myeloid cancers and impair the hydroxylation of 5-methylcytosine.1 In a study of 104 pediatric AML patients only 4 patients (3.8%) were found with somatic mutations of TET2.2 There is, however, growing evidence that germline single-nucleotide polymorphisms (SNPs) may also predict outcomes.3, 4 Here we demonstrate that somatic mutations of TET2 are rare in pediatric AML, but we present novel evidence that the TET2 SNP rs2454206 (I1762V) is a prognostic marker for outcome in pediatric AML.

This study included 403 patients treated on Children’s Cancer Group study CCG-2961 (N=169) or COG AAML03P1 (N=234). The CCG-2961 cohort was used as a discovery set and the prognostic biomarker (TET2 SNP rs2454206) was validated in the COG AAML03P1 cohort. Outcomes analyzed included overall survival (OS), event-free survival, relapse rate and non-relapse mortality (NRM). Hazard ratios were determined in univariate and multivariate analyses including risk group (Supplementary Material).

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Acknowledgements

This work was supported by grants no. U10-CA98543 (Chair's Grant), U10-CA98413 (Statistics and Data Center Grant), U24-CA114766 (Children’s Oncology Group), NCI R01-CA114563 (S.M.), and NCI R21-CA104964-02 (S.M.). MK was supported in part by the National Institutes of Health under the Ruth L. Kirschstein National Research Service Award T32CA009351. The contents of this report are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. We thank V. Shankar, Ph.D. (St Jude Research Hospital) for scientific editing. We thank the patients and their families who consented to use of the specimens used in the conduct of this research and the Children’s Oncology Group AML Reference Laboratory for providing these specimens.

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Authors and Affiliations

  1. Department of Pediatrics, Division of Hematology/Oncology, University of Alabama at Birmingham, Birmingham, AL, USA

    M A Kutny

  2. Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    T A Alonzo

  3. Department of Medicine, The University of Chicago, Chicago, IL, USA

    E R Gamazon, A Konkashbaev & N J Cox

  4. Department of Medicine, Division of Genetic Medicine, Vanderbilt University, Nashville, TN, USA

    E R Gamazon, A Konkashbaev & N J Cox

  5. Children's Oncology Group, Monrovia, CA, USA

    R B Gerbing

  6. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    D Geraghty & S Meshinchi

  7. Oncology, Children's Hospital of Philadelphia, Philadelphia, PA, USA

    B Lange & R Aplenc

  8. Department of Pathology, The Ohio State University, Columbus, OH, USA

    N A Heerema

  9. The Division of Haematology/Oncology and Child Health Evaluative Sciences, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada

    L Sung

  10. Amgen, Inc, Thousand Oaks, CA, USA

    J Franklin

  11. Department of Pathology, St Jude Children's Research Hospital, Memphis, TN, USA

    S C Raimondi

  12. Division of Laboratory Medicine, University of Minnesota Medical Center-Fairview, Minneapolis, MN, USA

    B A Hirsch

  13. Department of Pediatrics, The University of Chicago, Chicago, IL, USA

    K Onel

  14. Division of Hematology/Oncology, Children's Mercy Hospital and Clinics, Kansas City, MO, USA

    A S Gamis

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  1. M A Kutny
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Correspondence to M A Kutny.

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Competing interests

J.F. is employed by Amgen Inc (Thousand Oaks, CA, USA). The remaining authors declare no competing financial interests.

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Kutny, M., Alonzo, T., Gamazon, E. et al. Ethnic variation of TET2 SNP rs2454206 and association with clinical outcome in childhood AML: a report from the Children’s Oncology Group. Leukemia 29, 2424–2426 (2015). https://doi.org/10.1038/leu.2015.171

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