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.

  • Letter to the Editor
  • Published:

Concomitant analysis of EZH2 and ASXL1 mutations in myelofibrosis, chronic myelomonocytic leukemia and blast-phase myeloproliferative neoplasms

Leukemia volume 25, pages 1200–1202 (2011)Cite this article

Subjects

Somatic mutations in EZH2 and ASXL1 have recently been reported in myelofibrosis (MF) and chronic myelomonocytic leukemia (CMML).1, 2, 3, 4 The current study examines the frequency of these mutations in a larger cohort of patients with these diseases and their correlation with other myeloproliferative neoplasm (MPN)-associated mutations and disease phenotype. Given that many earlier studies of mutations in ASXL1 did not utilize paired normal tissue, and have largely reported mutations occurring in exon 12 (refs 3, 5, 6, 7), we also present previously unpublished/unannotated data regarding novel somatic missense mutations/single-nucleotide polymorphisms (SNPs) throughout the coding region of ASXL1.

Study samples from 143 patients were recruited from the Mayo Clinic, Rochester, MN, USA (n=94; 46 primary MF, 22 post-polycythemia vera/essential thrombocythemia myelofibrosis (post-PV/ET MF), 11 blast-phase MPN and 15 CMML), Harvard Institutes (n=25 primary myelofibrosis (PMF) with paired normal tissue) and MD Anderson Cancer Center (n=24 CMML with paired normal tissue). High throughput DNA resequencing was used to screen bone marrow (Mayo and MD Anderson samples) or granulocyte (Harvard MPD cohort)-derived DNA coding regions of EZH2 (NM_015338), ASXL1 (NM_004456) and TET2 (NM_017628), as well as the regions of known mutations in IDH1, IDH2, JAK2 and MPL in all samples. CMML samples were also screened for known FLT3, K Ras and N Ras mutations. Nonsynonymous alterations not found in SNP databases (dbSNP) were annotated as somatic mutations or SNPs on the basis of sequence analysis of matched-germ line buccal swab DNA. Nonsynonymous alterations not in dbSNP nor determined to be somatic in paired samples or in recently reported data were censored.

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

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Figure 1

References

  1. Gelsi-Boyer V, Trouplin V, Roquain J, Adelaide J, Carbuccia N, Esterni B et al. ASXL1 mutation is associated with poor prognosis and acute transformation in chronic myelomonocytic leukaemia. Br J Haematol 2010; 151: 365–375.

    Article  CAS  Google Scholar 

  2. Ernst T, Chase AJ, Score J, Hidalgo-Curtis CE, Bryant C, Jones AV et al. Inactivating mutations of the histone methyltransferase gene EZH2 in myeloid disorders. Nat Genet 2010; 42: 722–726.

    Article  CAS  Google Scholar 

  3. Carbuccia N, Murati A, Trouplin V, Brecqueville M, Adelaide J, Rey J et al. Mutations of ASXL1 gene in myeloproliferative neoplasms. Leukemia 2009; 23: 2183–2186.

    Article  CAS  Google Scholar 

  4. Boultwood J, Perry J, Zaman R, Fernandez-Santamaria C, Littlewood T, Kusec R et al. High-density single nucleotide polymorphism array analysis and ASXL1 gene mutation screening in chronic myeloid leukemia during disease progression. Leukemia 2010; 24: 1139–1145.

    Article  CAS  Google Scholar 

  5. Szpurka H, Jankowska AM, Makishima H, Bodo J, Bejanyan N, Hsi ED et al. Spectrum of mutations in RARS-T patients includes TET2 and ASXL1 mutations. Leuk Res 2010; 34: 969–973.

    Article  CAS  Google Scholar 

  6. Perez B, Kosmider O, Cassinat B, Renneville A, Lachenaud J, Kaltenbach S et al. Genetic typing of CBL, ASXL1, RUNX1, TET2 and JAK2 in juvenile myelomonocytic leukaemia reveals a genetic profile distinct from chronic myelomonocytic leukaemia. Br J Haematol 2010; 151: 460–468.

    Article  CAS  Google Scholar 

  7. Carbuccia N, Trouplin V, Gelsi-Boyer V, Murati A, Rocquain J, Adelaide J et al. Mutual exclusion of ASXL1 and NPM1 mutations in a series of acute myeloid leukemias. Leukemia 2010; 24: 469–473.

    Article  CAS  Google Scholar 

  8. Passamonti F, Cervantes F, Vannucchi AM, Morra E, Rumi E, Cazzola M et al. Dynamic International Prognostic Scoring System (DIPSS) predicts progression to acute myeloid leukemia in primary myelofibrosis. Blood 2010; 116: 2857–2858.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported in part by grants from the Gabrielle's Angel Foundation and from the Starr Cancer Consortium to RLL. RLL is an Early Career Award Recipient of the Howard Hughes Medical Institute and is a Geoffrey Beene Junior Faculty Chair at Memorial Sloan Kettering Cancer Center.

Author information

Authors and Affiliations

  1. Human Oncology and Pathogenesis Program Memorial Sloan Kettering Cancer Center, New York, NY, USA

    O Abdel-Wahab, J Patel, A Heguy & R L Levine

  2. Department of Medicine, Leukemia Service, Memorial Sloan Kettering Cancer,

    O Abdel-Wahab & R L Levine

  3. Center, New York, NY, USA

    O Abdel-Wahab & R L Levine

  4. Division of Hematology, Mayo Clinic, Rochester, MN, USA

    A Pardanani, T Lasho & A Tefferi

  5. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

    M Wadleigh

  6. Division of Leukemia, M.D. Anderson Cancer, Houston, TX, USA

    M Beran

  7. Merck & Co., Incorporated, North Wales, PA, USA

    D G Gilliland

Authors
  1. O Abdel-Wahab
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A Pardanani
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J Patel
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M Wadleigh
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. T Lasho
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A Heguy
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M Beran
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. D G Gilliland
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. R L Levine
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. A Tefferi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to O Abdel-Wahab.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Abdel-Wahab, O., Pardanani, A., Patel, J. et al. Concomitant analysis of EZH2 and ASXL1 mutations in myelofibrosis, chronic myelomonocytic leukemia and blast-phase myeloproliferative neoplasms. Leukemia 25, 1200–1202 (2011). https://doi.org/10.1038/leu.2011.58

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/leu.2011.58

This article is cited by

Search

Advanced search

Quick links