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:

JAK2V617F mutational frequency in polycythemia vera: 100%, >90%, less?

Leukemia volume 20, page 2067 (2006)Cite this article

A somatic point mutation in the tyrosine kinase JAK2 (1849 G to T) has been described in myeloproliferative diseases (MPD), resulting in a non-synonymous amino-acid substitution (V to F) at position 617. This mutation (JAK2V617F) is located in the JH2 pseudo-kinase auto-inhibitory domain, rendering the enzyme constitutively active and leading to cytokine hypersensitivity and erythrocytosis in mice.1 There is considerable variation in the reports of JAK2V617F frequency in MPD, with incidence rates of 23–57% in essential thrombocythemia, 35–57% in idiopathic myelofibrosis and 65–97% in polycythemia vera (PV).2 Of particular interest is the expression of JAK2V617F mutation in PV, with its hallmark of erythrocytosis, which involves the JAK2-signaling pathway. Possible reasons for discrepancies in the observed mutation frequency in PV by different research groups include (1) differences in assay sensitivity,3 (2) diagnostic inaccuracy and (3) treatment effect.4 In order to examine these possibilities, we have re-examined 17 previously published JAK2V617F-negative PV cases, including nine from the Mayo Clinic,5, 6 four from the MD Anderson Cancer Center (MDACC)7 and four from the Weill Medical College.8 Among the nine Mayo Clinic cases, the diagnosis was inaccurate in four and questionable in one. Repeat testing with more sensitive techniques revealed the presence of the mutation in three of the remaining four patients. In the last patient, there was not enough material for re-testing. Among the four MDACC cases, two were positive for JAK2V617F mutation on re-testing using a more sensitive technique; mutation screening in the other two patients was performed at the time of leukemic transformation and the historical diagnosis of PV had not been well documented. Of the four cases reported by the Weill Medical College researchers, two were receiving interferon-α therapy for several years before testing for the mutation, and two had interferon discontinued 2 years before testing for JAK2 because of excellent clinical response. Thus, treatment could have resulted in the suppression of the mutant clone.4 Therefore, we conclude that a diagnosis of ‘PV’ in the absence of the JAK2V617F warrants a re-evaluation that takes into account the possibility for misdiagnosis, treatment-related effect and an insufficiently sensitive mutation screening assay. Once these three issues are addressed, it seems likely that the JAK2V617F mutation may be present in virtually all PV patients.

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. James C, Ugo V, Le Couedic JP, Staerk J, Delhommeau F, Lacout C et al. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature 2005; 434: 1144–1148.

    Article  CAS  Google Scholar 

  2. Nelson ME, Steensma DP . JAK2 V617F in myeloid disorders: what do we know now, and where are we headed? Leuk Lymphoma 2006; 47: 177–194.

    Article  CAS  Google Scholar 

  3. Greiner TC . Diagnostic assays for the JAK2 V617F mutation in chronic myeloproliferative disorders. Am J Clin Pathol 2006; 125: 651–653.

    Article  CAS  Google Scholar 

  4. Jones AV, Silver RT, Waghorn K, Curtis C, Kreil S, Zoi K et al. Minimal molecular response in polycythemia vera patients treated with imatinib or interferon alpha. Blood 2006; 107: 3339–3341.

    Article  CAS  Google Scholar 

  5. Tefferi A, Lasho TL, Schwager SM, Strand JS, Elliott M, Mesa R et al. The clinical phenotype of wild-type, heterozygous, and homozygous JAK2V617F in polycythemia vera. Cancer 2006; 106: 631–635.

    Article  CAS  Google Scholar 

  6. McClure R, Mai M, Lasho T . Validation of two clinically useful assays for evaluation of JAK2 V617F mutation in chronic myeloproliferative disorders. Leukemia 2006; 20: 168–171.

    Article  CAS  Google Scholar 

  7. Jelinek J, Oki Y, Gharibyan V, Bueso-Ramos C, Prchal JT, Verstovsek S et al. JAK2 mutation 1849G>T is rare in acute leukemias but can be found in CMML, Philadelphia chromosome-negative CML, and megakaryocytic leukemia. Blood 2005; 106: 3370–3373.

    Article  CAS  Google Scholar 

  8. Jones AV, Kreil S, Zoi K, Waghorn K, Curtis C, Zhang L et al. Widespread occurrence of the JAK2 V617F mutation in chronic myeloproliferative disorders. Blood 2005; 106: 2162–2168.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    S Verstovsek

  2. Leukemia and Myeloproliferative Center, Weill Medical College of Cornell University, New York, NY, USA

    R T Silver

  3. Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury, UK

    N C P Cross

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

    A Tefferi

Authors
  1. S Verstovsek
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R T Silver
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. N C P Cross
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A Tefferi
    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

Verstovsek, S., Silver, R., Cross, N. et al. JAK2V617F mutational frequency in polycythemia vera: 100%, >90%, less?. Leukemia 20, 2067 (2006). https://doi.org/10.1038/sj.leu.2404379

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.leu.2404379

This article is cited by

Search

Advanced search

Quick links