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Chronic Myeloproliferative Neoplasias

TET2 mutations and their clinical correlates in polycythemia vera, essential thrombocythemia and myelofibrosis

Leukemia volume 23, pages 905–911 (2009)Cite this article

Abstract

High-throughput DNA sequence analysis was used to screen for TET2 mutations in bone marrow-derived DNA from 239 patients with BCR-ABL-negative myeloproliferative neoplasms (MPNs). Thirty-two mutations (19 frameshift, 10 nonsense, 3 missense; mostly involving exons 4 and 12) were identified for an overall mutational frequency of ∼13%. Specific diagnoses included polycythemia vera (PV; n=89), essential thrombocythemia (ET; n=57), primary myelofibrosis (PMF; n=60), post-PV MF (n=14), post-ET MF (n=7) and blast phase PV/ET/MF (n=12); the corresponding mutational frequencies were ∼16, 5, 17, 14, 14 and 17% (P=0.50). Mutant TET2 was detected in ∼17 and ∼7% of JAK2V617F-positive and -negative cases, respectively (P=0.04). However, this apparent clustering of the two mutations was accounted for by an independent association between mutant TET2 and advanced age; mutational frequency was ∼23% in patients ⩾60 years old versus ∼4% in younger patients (P<0.0001). The presence of mutant TET2 did not affect survival, leukemic transformation or thrombosis in either PV or PMF; a correlation with hemoglobin <10 g per 100 ml in PMF was noted (P=0.05). We conclude that TET2 mutations occur in both JAK2V617F-positive and -negative MPN, are more prevalent in older patients, display similar frequencies across MPN subcategories and disease stages, and hold limited prognostic relevance.

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Acknowledgements

Adriana Heguy and Igor Dolgalev from Memorial Sloan-Kettering Cancer Center, New York, NY, USA are acknowledged for their assistance with sequence analysis. This study was supported in part by grants from the Myeloproliferative Disorders Foundation, Chicago, IL, USA. DGG is an investigator of the Howard Hughes Medical Institute and is a Doris Duke Charitable Foundation Distinguished Clinical Scientist. RLL is an Early Career Award recipient of the Howard Hughes Medical Institute, a Clinical Scientist Development Award recipient of the Doris Duke Charitable Foundation and is the Geoffrey Beene Junior Chair at Memorial Sloan Kettering Cancer Center.

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Authors and Affiliations

  1. Divisions of Hematology and Hematopathology, Departments of Medicine and Laboratory Medicine, Mayo Clinic, Rochester, MN, USA

    A Tefferi, A Pardanani, K-H Lim, T L Lasho, N Gangat, C M Finke, S Schwager, C-Y Li, C A Hanson & R Mesa

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

    K-H Lim

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

    O Abdel-Wahab, J Patel & R L Levine

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

    O Abdel-Wahab & R L Levine

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

    A Mullally & D G Gilliland

  6. INSERM E0210, Hopital Necker,

    O Bernard

  7. APHP Laboratoire d'Hématologie, Hôpital Cochin

    O Bernard

  8. Université Paris V, Paris, France

    O Bernard

  9. INSERM U790, Institut Gustave Roussy, Villejuif, France

    F Delhommeau & W Vainchenker

  10. The Howard Hughes Medical Institute, Boston, MA, USA

    D G Gilliland

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  1. A Tefferi
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Correspondence to A Tefferi or R L Levine.

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Tefferi, A., Pardanani, A., Lim, KH. et al. TET2 mutations and their clinical correlates in polycythemia vera, essential thrombocythemia and myelofibrosis. Leukemia 23, 905–911 (2009). https://doi.org/10.1038/leu.2009.47

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