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Acute myeloid leukemia in the elderly is characterized by a distinct genetic and epigenetic landscape

Leukemia volume 31, pages 1640–1644 (2017)Cite this article

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Acute myeloid leukemia (AML) is a disease of the elderly population. With a median age of 71 years, elderly patients with AML show poor survival probabilities.1, 2 This can be attributed to several disease characteristics, most importantly to adverse cytogenetic aberrations occurring more frequently in older than in younger AML patients.3, 4 Nevertheless, within defined cytogenetic risk groups, elderly AML patients still have a higher relapse rate and show an inferior outcome compared to younger patients of the same risk group.3, 5 Though complex patterns of molecular alterations have been characterized, comprehensive studies are lacking to determine genomic and epigenomic alterations in elderly AML that might contribute to its distinct poor prognosis. Thus, we investigated genetic alterations and global epigenetic changes in elderly AML to define their molecular profiles.

In a comprehensive approach, we analyzed a large set of candidate genes (n=555) by targeted NGS, using an Illumina HiSeq2000 (San Diego, CA, USA; Supplementary Methods) with high coverage of targets (408±164 reads). We sequenced DNA from the bone marrow of 93 elderly AML patients (65 to 90 years) enrolled in the Study Alliance Leukemia registry (SAL), which represented well an average population based AML cohort2 (Supplementary Table 1). In total, 814 mutations were detected in 281 candidate genes (Supplementary Table 2, Supplementary Figure 1), with a median number of seven genes mutated per patient (Supplementary Figure 2A). Most of the altered genes displayed mutations in a possible founding clone (Supplementary Figure 2B).

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Acknowledgements

We thank Liliana H Mochmann for the critical reading of the manuscript. This study was supported by Else Kröner-Fresenius-Stiftung (2013A153), the German Cancer Consortium (Deutsches Konsortium fur Translationale Krebsforschung DKTK, Heidelberg, Germany), the Deutsche Krebshilfe (Mildred Scheel Stiftungsprofessur, CDB) and the Deutsche Forschungsgemeinschaft (DFG EXC 1003, WEB). PS was supported by the Berlin School of Integrative Oncology (BSIO).

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Authors and Affiliations

  1. Department of Hematology and Oncology, Charité University Hospital, Berlin, Germany

    P Silva, M Neumann, M P Schroeder, C Schlee, K Isaakidis, J Ortiz-Tanchez, L R Fransecky, T Hartung & C D Baldus

  2. German Cancer Consortium (DKTK), Heidelberg, Germany

    M Neumann, S Vosberg, C Thiede, G Ehninger, H Serve, P A Greif, C Röllig & C D Baldus

  3. German Cancer Research Center (DKFZ), Heidelberg, Germany

    M Neumann, S Vosberg, C Thiede, G Ehninger, H Serve, P A Greif, C Röllig & C D Baldus

  4. Department of Internal Medicine 3, Ludwig Maximilians University, Munich, Germany

    S Vosberg & P A Greif

  5. Labor Berlin Charité Vivantes GmbH, Berlin, Germany

    S Türkmen

  6. Institute of Medical Genetics and Human Genetics, Charité University Medicine, Campus Virchow-Klinikum, Berlin, Germany

    S Türkmen

  7. Laboratory for Functional Genome Analysis, Gene Center, Ludwig Maximilians University, Munich, Germany

    A Graf, S Krebs & H Blum

  8. Department of Medicine IV, Hematology and Oncology, University Hospital of Halle (Saale), Halle, Germany

    C Müller-Tidow

  9. Department of Internal Medicine I, University Hospital Carl-Gustav-Carus, Dresden, Germany

    C Thiede, G Ehninger & C Röllig

  10. Department of Medicine II, Hematology/Oncology, University Hospital Frankfurt, Frankfurt am Main, Germany

    H Serve

  11. Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain

    J Hecht

  12. Universitat Pompeu Fabra (UPF), Barcelona, Spain

    J Hecht

  13. Department of Medicine A, University Hospital Münster, Münster, Germany

    W E Berdel

Authors
  1. P Silva
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  2. M Neumann
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  3. M P Schroeder
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  6. K Isaakidis
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  7. J Ortiz-Tanchez
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  8. L R Fransecky
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  10. S Türkmen
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  11. A Graf
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  12. S Krebs
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  13. H Blum
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  14. C Müller-Tidow
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  15. C Thiede
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  16. G Ehninger
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  17. H Serve
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  18. J Hecht
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  19. W E Berdel
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  20. P A Greif
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  21. C Röllig
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  22. C D Baldus
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Corresponding author

Correspondence to C D Baldus.

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The authors declare no conflict of interest.

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Supplementary Information accompanies this paper on the Leukemia website

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Silva, P., Neumann, M., Schroeder, M. et al. Acute myeloid leukemia in the elderly is characterized by a distinct genetic and epigenetic landscape. Leukemia 31, 1640–1644 (2017). https://doi.org/10.1038/leu.2017.109

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