Skip to main content

Thank you for visiting nature.com. 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.

Distinct clinical and biological implications of various DNMT3A mutations in myeloid neoplasms

Subjects

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1

References

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Ribeiro AFT, Pratcorona M, Erpelinck-Verschueren C, Rockova V, Sanders M, Abbas S et al. Mutant DNMT3A: a marker of poor prognosis in acute myeloid leukemia. Blood 2012; 119: 5824–5831.

    Article  CAS  PubMed  Google Scholar 

  3. Roller A, Grossmann V, Bacher U, Poetzinger F, Weissmann S, Nadarajah N et al. Landmark analysis of DNMT3A mutations in hematological malignancies. Leukemia 2013; 27: 1573.

    Article  CAS  PubMed  Google Scholar 

  4. Shih AH, Abdel-Wahab O, Patel JP, Levine RL . The role of mutations in epigenetic regulators in myeloid malignancies. Nat Rev Cancer 2012; 12: 599–612.

    Article  CAS  PubMed  Google Scholar 

  5. Walter MJ, Ding L, Shen D, Shao J, Grillot M, McLellan M et al. Recurrent DNMT3A mutations in patients with myelodysplastic syndromes. Leukemia 2011; 25: 1153–1158.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Abdel-Wahab O, Pardanani A, Rampal R, Lasho T, Levine R, Tefferi A . DNMT3A mutational analysis in primary myelofibrosis, chronic myelomonocytic leukemia and advanced phases of myeloproliferative neoplasms. Leukemia 2011; 25: 1219.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Genovese G, Kähler AK, Handsaker RE, Lindberg J, Rose SA, Bakhoum SF et al. Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence. N Engl J Med 2014; 371: 2477–2487.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Jaiswal S, Fontanillas P, Flannick J, Manning A, Grauman PV, Mar BG et al. Age-related clonal hematopoiesis associated with adverse outcomes. N Engl J Med 2014; 371: 2488–2498.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Yang L, Rau R, Goodell MA . DNMT3A in haematological malignancies. Nat Rev Cancer 2015; 15: 152–165.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Russler-Germain DA, Spencer DH, Young MA, Lamprecht TL, Miller CA, Fulton R et al. The R882H DNMT3A mutation associated with AML dominantly inhibits wild-type DNMT3A by blocking its ability to form active tetramers. Cancer Cell 2014; 25: 442–454.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Xie M, Lu C, Wang J, McLellan MD, Johnson KJ, Wendl MC et al. Age-related mutations associated with clonal hematopoietic expansion and malignancies. Nat Med 2014; 20: 1472–1478.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Challen GA, Sun D, Jeong M, Luo M, Jelinek J, Berg JS et al. Dnmt3a is essential for hematopoietic stem cell differentiation. Nat Genet 2012; 44: 23–31.

    Article  CAS  Google Scholar 

  13. Holz-Schietinger C, Matje DM, Reich NO . Mutations in DNA methyltransferase (DNMT3A) observed in acute myeloid leukemia patients disrupt processive methylation. J Biol Chem 2012; 287: 30941–30951.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Kim SJ, Zhao H, Hardikar S, Singh AK, Goodell MA, Chen T . A DNMT3A mutation common in AML exhibits dominant-negative effects in murine ES cells. Blood 2013; 122: 4086–4089.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Makishima H, Yoshizato T, Yoshida K, Sekeres MA, Radivoyevitch T, Suzuki H et al. Dynamics of clonal evolution in myelodysplastic syndromes. Nat Genet 2016; 49: 204–212.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by the EPE1509JM - Edward P Evans Foundation, R01HL123904 – NHLBI, R01HL118281 – NHLBI, R01HL128425 – NHLBI.

Author contributions

SKB designed the research, analyzed the data, and wrote the paper, MA, TB, YN, VA, VV, AN, SM, HEC, MAS helped with interpretation of the results and edited the manuscript, KT collected the clinical data and CH, BPP performed research procedures, TR helped with statistics, JPM designed the study and wrote the manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to J P Maciejewski.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies this paper on the Leukemia website

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Balasubramanian, S., Aly, M., Nagata, Y. et al. Distinct clinical and biological implications of various DNMT3A mutations in myeloid neoplasms. Leukemia 32, 550–553 (2018). https://doi.org/10.1038/leu.2017.295

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/leu.2017.295

This article is cited by

Search

Quick links