Mutations in the DNMT3A exon 23 independently predict poor outcome in older patients with acute myeloid leukemia: a SWOG report

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References

  1. 1

    Thiede C, Steudel C, Mohr B, Schaich M, Schäkel U, Platzbecker U et al. Analysis of FLT3-activating mutations in 979 patients with acute myelogenous leukemia: association with FAB subtypes and identification of subgroups with poor prognosis. Blood 2002; 99: 4326–4335.

  2. 2

    Falini B, Mecucci C, Tiacci E, Alcalay M, Rosati R, Pasqualucci L et al. GIMEMA Acute Leukemia Working Party. Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype. N Engl J Med 2005; 352: 254–266.

  3. 3

    Ho PA, Alonzo TA, Gerbing RB, Pollard J, Stirewalt DL, Hurwitz C et al. Prevalence and prognostic implications of CEBPA mutations in pediatric acute myeloid leukemia (AML): a report from the Children′s Oncology Group. Blood 2009; 113: 6558–6566.

  4. 4

    Yamashita Y, Yuan J, Suetake I, Suzuki H, Ishikawa Y, Choi YL et al. Array-based genomic resequencing of human leukemia. Oncogene 2010; 29: 3723–3731.

  5. 5

    Ley TJ, Ding L, Walter MJ, McLellan MD, Lamprecht T, Larson DE et al. DNMT3A-Mut in acute myeloid leukemia. N Engl J Med 2010; 363: 2424–2433.

  6. 6

    Yan XJ, Xu J, Gu ZH, Pan CM, Lu G, Shen Y et al. Exome sequencing identifies somatic mutations of DNA methyltransferase gene DNMT3A in acute monocytic leukemia. Nat Genet 2011; 43: 309–315.

  7. 7

    Thol F, Damm F, Lüdeking A, Winschel C, Wagner K, Morgan M et al. Incidence and prognostic influence of DNMT3A mutations in acute myeloid leukemia. J Clin Oncol 2011; 29: 2889–2896.

  8. 8

    Shen Y, Zhu YM, Fan X, Shi JY, Wang QR, Yan XJ et al. Gene mutation patterns and their prognostic impact in a cohort of 1185 patients with acute myeloid leukemia. Blood 2011; 118: 5593–5603.

  9. 9

    Marková J, Michková P, Burčková K, Březinová J, Michalová K, Dohnalová A et al. Prognostic impact of DNMT3A mutations in patients with intermediate cytogenetic risk profile acute myeloid leukemia. Eur J Haematol 2012; 88: 128–135.

  10. 10

    Lin J, Yao DM, Qian J, Chen Q, Qian W, Li Y et al. Recurrent DNMT3A R882 mutations in Chinese patients with acute myeloid leukemia and myelodysplastic syndrome. PLoS One 2011; 6: e26906.

  11. 11

    Hou HA, Kuo YY, Liu CY, Chou WC, Lee MC, Chen CY et al. DNMT3A mutations in acute myeloid leukemia: stability during disease evolution and clinical implications. Blood 2012; 119: 559–568.

  12. 12

    Anderson JE, Kopecky KJ, Willman CL, Head D, O′Donnell MR, Luthardt FW et al. Outcome after induction chemotherapy for older patients with acute myeloid leukemia is not improved with mitoxantrone and etoposide compared to cytarabine and daunorubicin: a Southwest Oncology Group study. Blood 2002; 100: 3869–3876.

  13. 13

    Godwin JE, Kopecky KJ, Head DR, Willman CL, Leith CP, Hynes HE et al. A double-blind placebo-controlled trial of granulocyte colony-stimulating factor in elderly patients with previously untreated acute myeloid leukemia: a Southwest oncology group study (9031). Blood 1998; 91: 3607–3615.

  14. 14

    Slovak ML, Kopecky KJ, Cassileth PA, Harrington DH, Theil KS, Mohamad A et al. Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group study. Blood 2000; 96: 4075–4083.

  15. 15

    Ho PA, Kutny MA, Alonzo TA, Gerbing RB, Joaquin J, Raimondi SC, Gamis AS, Meshinchi S . Leukemic mutations in the methylation-associated genes DNMT3A and IDH2 are rare events in pediatric AML: a report from the Children′s Oncology Group. Pediatr Blood Cancer 2011; 57: 204–209.

  16. 16

    Röllig C, Bornhäuser M, Thiede C, Taube F, Kramer M et al. Long-term prognosis of acute myeloid leukemia according to the new genetic risk classification of the European LeukemiaNet recommendations: evaluation of the proposed reporting system. J Clin Oncol 2011; 29: 2758–2765.

  17. 17

    Marcucci G, Metzeler KH, Schwind S, Becker H, Maharry K et al. Age-related prognostic impact of different types of DNMT3A mutations in adults with primary cytogenetically normal acute myeloid leukemia. J Clin Oncol 2012; 30: 742–750.

  18. 18

    Metzeler KH, Walker A, Geyer S, Garzon R, Klisovic RB et al. DNMT3A mutations and response to the hypomethylating agent decitabine in acute myeloid leukemia. Leukemia 2012; 26: 1106–1107.

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Acknowledgements

We thank the patients and families who consented to the use of biologic specimens in these trials and the AML Reference Laboratories of the COG and SWOG for providing diagnostic specimens. This investigation was supported in part by the following PHS Cooperative Agreement grant numbers awarded by the National Cancer Institute, Cancer Therapy Evaluation Program, DHHS: CA32102, CA38926, CA20319, CA12213.

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Correspondence to F Ostronoff.

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The authors declare no conflict of interest.

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FO designed and performed the research, analyzed data and wrote the manuscript; MO performed statistical analyses and edited the manuscript; PAH, DEG, SHP, JEG, CLW, JPR and FRA performed the research and edited the manuscript; SM designed the research, analyzed data and edited the manuscript.

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Ostronoff, F., Othus, M., Ho, P. et al. Mutations in the DNMT3A exon 23 independently predict poor outcome in older patients with acute myeloid leukemia: a SWOG report. Leukemia 27, 238–241 (2013). https://doi.org/10.1038/leu.2012.168

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