Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Acute Myeloid Leukemia

Germline alterations in a consecutive series of acute myeloid leukemia

This is a preview of subscription content

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Fig. 1


  1. 1.

    Godley LA, Shimamura A. Genetic predisposition to hematologic malignancies: management and surveillance. Blood. 2017;130:424–32.

    CAS  Article  Google Scholar 

  2. 2.

    Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127:2391–405.

    CAS  Article  Google Scholar 

  3. 3.

    Dohner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Buchner T, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017;129:424–47.

    Article  Google Scholar 

  4. 4.

    Churpek JE, Pyrtel K, Kanchi KL, Shao J, Koboldt D, Miller CA, et al. Genomic analysis of germ line and somatic variants in familial myelodysplasia/acute myeloid leukemia. Blood. 2015;126:2484–90.

    CAS  Article  Google Scholar 

  5. 5.

    Cardoso SR, Ryan G, Walne AJ, Ellison A, Lowe R, Tummala H, et al. Germline heterozygous DDX41 variants in a subset of familial myelodysplasia and acute myeloid leukemia. Leukemia. 2016;30:2083–6.

    CAS  Article  Google Scholar 

  6. 6.

    Boocock GR, Morrison JA, Popovic M, Richards N, Ellis L, Durie PR, et al. Mutations in SBDS are associated with Shwachman-Diamond syndrome. Nat Genet. 2003;33:97–101.

    CAS  Article  Google Scholar 

  7. 7.

    Lindsley RC, Saber W, Mar BG, Redd R, Wang T, Haagenson MD, et al. Prognostic mutations in myelodysplastic syndrome after stem-cell transplantation. N Engl J Med. 2017;376:536–47.

    CAS  Article  Google Scholar 

  8. 8.

    Valli R, De Paoli E, Nacci L, Frattini A, Pasquali F, Maserati E. Novel recurrent chromosome anomalies in Shwachman-Diamond syndrome. Pediatr Blood Cancer. 2017;64:e26454.

    Article  Google Scholar 

  9. 9.

    Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17:405–24.

    Article  Google Scholar 

  10. 10.

    Brown AL, Churpek JE, Malcovati L, Dohner H, Godley LA. Recognition of familial myeloid neoplasia in adults. Semin Hematol. 2017;54:60–8.

    Article  Google Scholar 

  11. 11.

    Tesi B, Davidsson J, Voss M, Rahikkala E, Holmes TD, Chiang SCC, et al. Gain-of-function SAMD9L mutations cause a syndrome of cytopenia, immunodeficiency, MDS, and neurological symptoms. Blood. 2017;129:2266–79.

    CAS  Article  Google Scholar 

  12. 12.

    Lu C, Xie M, Wendl MC, Wang J, Mclellan MD, Leiserson MD, et al. Patterns and functional implications of rare germline variants across 12 cancer types. Nat Commun. 2015;6:10086.

    CAS  Article  Google Scholar 

  13. 13.

    Churpek JE, Marquez R, Neistadt B, Claussen K, Lee MK, Churpek MM, et al. Inherited mutations in cancer susceptibility genes are common among survivors of breast cancer who develop therapy-related leukemia. Cancer. 2016;122:304–11.

    CAS  Article  Google Scholar 

  14. 14.

    David L, Fernandez-Vidal A, Bertoli S, Grgurevic S, Lepage B, Deshaies D, et al. CHK1 as a therapeutic target to bypass chemoresistance in AML. Sci Signal. 2016;9:ra90.

    Article  Google Scholar 

  15. 15.

    Zare F, Dow M, Monteleone N, Hosny A, Nabavi S. An evaluation of copy number variation detection tools for cancer using whole exome sequencing data. BMC Bioinforma. 2017;18:286.

    Article  Google Scholar 

Download references


This study was funded by grants from the Academy of Finland (#274474, #312492, and #284538), the Sigrid Juselius Foundation, Helsinki University Hospital Comprehensive Cancer Research Funding, and The Finnish Funding Agency for Technology and Innovation (TEKES). We are extremely grateful to patients who participated and thus made this study possible. We thank FuGU and the FIMM Technology Center for excellent exome/Sanger sequencing services; Minna Suvela, Siv Knaappila, Annukka Ruokolainen, and Pihla Siipola for excellent technical assistance. The Aaltonen laboratory, especially Riku Katainen, is thanked for help in bioinformatics and the exome control files.

Author contributions

OK and UW-K designed the study. UW-K collected the clinical data, analyzed the results, and drafted the manuscript. EAMH analyzed the exome data, validated the mutations, and drafted the manuscript together with OK and UW-K. EP brought new ideas to the data analysis and contributed to the statistical analyses. JS, KK, and CH organized the exome sequencing at FIMM. KP organized the exome sequencing and major funding for the project. All authors have read and approved the manuscript.

Author information



Corresponding author

Correspondence to Outi Kilpivaara.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Electronic supplementary material

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Wartiovaara-Kautto, U., Hirvonen, E.A.M., Pitkänen, E. et al. Germline alterations in a consecutive series of acute myeloid leukemia. Leukemia 32, 2282–2285 (2018).

Download citation

Further reading


Quick links