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:

Detection of mutant TET2 in myeloid malignancies other than myeloproliferative neoplasms: CMML, MDS, MDS/MPN and AML

Leukemia volume 23, pages 1343–1345 (2009)Cite this article

TET2 (TET oncogene family member 2) is a putative tumor suppressor gene located at chromosome 4q24.1 Delhommeau et al.1 were the first to report the occurrence of TET2 mutations in myeloproliferative neoplasms (MPN); the authors discovered frameshift, nonsense and missense TET2 mutations in approximately 14% of 181 patients with JAK2V617F-positive polycythemia vera, essential thrombocythemia or primary myelofibrosis (PMF). We subsequently confirmed this observation in a recent study of 239 patients and reported mutational frequencies of ∼16, ∼5 and ∼17% in polycythemia vera, essential thrombocythemia and PMF, respectively.2 In the latter study, TET2 mutations were seen in both JAK2V617F-positive (∼17%) and negative (∼7%) cases and their frequency was similar in chronic and advanced phase disease.2 In another recent Leukemia paper,3 we reported an even higher TET2 mutational frequency of 29% in systemic mastocytosis (SM), a disease that is also formally classified as MPN.4 In this study, we looked for the presence of TET2 mutations in myeloid malignancies other than MPN, including chronic myelomonocytic leukemia (CMML), myelodysplastic syndrome (MDS), ‘MDS/MPN’ and acute myeloid leukemia (AML). We have also included some cases with MPN, unclassifiable (MPN-U).4

After approval by the Mayo Clinic institutional review board, study patients were selected on the basis of availability of stored bone marrow cells for DNA extraction and mutation analysis. Diagnoses were established on the basis of 2001 World Health Organization (WHO) criteria.5 Mutation screening for JAK2V617F (reverse transcription-PCR) was performed using bone marrow-derived cells, according to the earlier published methods.6 High-throughput DNA sequence analysis was used to screen for TET2 mutations in bone marrow-derived DNA as described earlier.2 A total of 50 patients were included in this study: 15 with CMML, 16 with MDS, 7 with secondary AML, 5 with de novo AML, 3 with MDS/MPN and 4 with MPN-U. The 15 patients with CMML included 10 with CMML-1 and 5 with CMML-2. The 16 MDS cases included 5 with refractory anemia/cytopenia (RA)/refractory cytopenia with multilineage dysplasia (RCMD), 5 with RA with ring sideroblasts (RARS)/RCMD-RS, 4 with RA with excess blasts (RAEB)-1/2 and 2 with del(5q). The seven secondary AML cases arose from antecedent MDS in five cases (including two therapy-related) and in one case each from MDS/MPN or CMML. The five de novo AML cases included AML-M7 (n=3), AML-M6 and AML-M3. The three MDS/MPN cases included one patient with RARS and thrombocytosis (RARS-T).

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

References

  1. Delhommeau F, Dupont S, James C, Masse A, le Couedic JP, Valle VD et al. TET2 is a novel tumor suppressor gene inactivated in myeloproliferative neoplasms: identification of a Pre-JAK2 V617F event. ASH Annual Meeting Abstracts 2008; 112: lba-3. Late-Breaking Abstract.

  2. Tefferi A, Pardanani A, Lim K-H, Abdel-Wahab O, Lasho TL, Patel J et al. TET2 mutations and their clinical correlates in polycythemia vera, essential thrombocythemia and myelofibrosis. Leukemia 2009, advance online publication, 5 March 2009; doi:10.1038/ leu.2009.47.

  3. Tefferi A, Levine RL, Lim K-H, Abdel-Wahab O, Lasho TL, Patel J et al. Frequent TET2 mutations in systemic mastocytosis: clinical, KITD816V and FIP1L1-PDGFRA correlates. Leukemia 2009, advance online publication, 5 March 2009; doi:10.1038/ leu.2009.37.

  4. Tefferi A, Vardiman JW . Classification and diagnosis of myeloproliferative neoplasms: the 2008 World Health Organization criteria and point-of-care diagnostic algorithms. Leukemia 2008; 22: 14–22.

    Article  CAS  Google Scholar 

  5. Jaffe ES, Harris NL, Stein H, Vardiman JW . World Health Organization Classification of Tumours of Hematopoietic and Lymphoid Tissues. IARC Press: Lyon, France, 2001, pp 1–351.

    Google Scholar 

  6. Tefferi A, Lasho TL, Huang J, Finke C, Mesa RA, Li CY et al. Low JAK2V617F allele burden in primary myelofibrosis, compared to either a higher allele burden or unmutated status, is associated with inferior overall and leukemia-free survival. Leukemia 2008; 22: 756–761.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Hematology and Hematopathology, Department of Medicine, Rochester, MN, USA

    A Tefferi, K-H Lim, T L Lasho, M M Patnaik, C A Hanson & A Pardanani

  2. Division of Hematopathology, Laboratory Medicine, Mayo Clinic, Rochester, MN, USA

    K-H Lim & C A Hanson

  3. Division of Hematology-Oncology, Mackay Memorial Hospital and Mackay Medicine, Nursing and Management College, Taipei, Taiwan

    K-H Lim

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

    O Abdel-Wahab, J Patel & R L Levine

  5. Department of Medicine, Leukemia Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    O Abdel-Wahab & R L Levine

  6. Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA

    D G Gilliland

  7. Howard Hughes Medical Institute, Boston, MA, USA

    D G Gilliland

Authors
  1. A Tefferi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. K-H Lim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. O Abdel-Wahab
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. T L Lasho
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J Patel
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M M Patnaik
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. C A Hanson
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. A Pardanani
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. D G Gilliland
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. R L Levine
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A Tefferi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tefferi, A., Lim, KH., Abdel-Wahab, O. et al. Detection of mutant TET2 in myeloid malignancies other than myeloproliferative neoplasms: CMML, MDS, MDS/MPN and AML. Leukemia 23, 1343–1345 (2009). https://doi.org/10.1038/leu.2009.59

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/leu.2009.59

This article is cited by

Search

Advanced search

Quick links