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 a new JAK2 D620E mutation in addition to V617F in a patient with polycythemia vera

Leukemia volume 20, pages 2210–2211 (2006)Cite this article

Recently, a unique point mutation in the JH2 domain of the Janus kinase 2 gene (JAK2) was identified in several chronic myeloid disorders. This mutation leads to a V617F substitution of phenylalanine for valine in the protein. Affected are more than 80% of polycythemia vera (PV), 40% of essential thrombocythemia (ET) and 40% of idiopathic myelofibrosis (CIM) patients.1

The non-receptor Janus tyrosine kinases are involved in the signalling pathways of erythropoietin (EPO), thrombopoietin (TPO) und granulocyte colony-stimulating factor (G-CSF) which mediate anti-apoptosis, cell cycle progression and growth. The V617F mutation is located in the JH2 pseudokinase domain of JAK2 which is involved in inhibition of the kinase activity.2 The mutant JAK2 is auto-phosphorylated in factor-dependent cell lines resulting in a cytokine independent activation of STAT5, ERK/MAP kinase and PI3K/AKT. Therefore, the V617F mutation is regarded as a gain-of-function mutation.3

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
Figure 2
Figure 3

References

  1. 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 

  2. Saharinen P, Vihinen M, Silvennoinen O . Autoinhibition of Jak2 tyrosine kinase is dependent on specific regions in its pseudokinase domain. Mol Biol Cell 2003; 14: 1448–1459.

    Article  CAS  Google Scholar 

  3. 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 

  4. 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 

  5. Baxter EJ, Scott LM, Campbell PJ, East C, Fourouclas N, Swanton S et al. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet 2005; 365: 1054–1061.

    Article  CAS  Google Scholar 

  6. Kralovics R, Skoda RC . Molecular pathogenesis of Philadelphia chromosome negative myeloproliferative disorders. Blood Rev 2005; 19: 1–13.

    Article  CAS  Google Scholar 

  7. Ishii T, Bruno E, Hoffman R, Xu M . Involvement of various hematopoietic cell lineages by the JAK2V617F mutation in polycythemia vera. Blood 2006, [E-pub ahead of print].

  8. Schnittger S, Bacher U, Kern W, Schroder M, Haferlach T, Schoch C . Report on two novel nucleotide exchanges in the JAK2 pseudokinase domain: D620E and E627E. Leukemia 2006, [E-pub ahead of print].

Download references

Author information

Authors and Affiliations

  1. Department of Oncology, Hematology, Immunology, Rheumatology and Pulmology, University of Tübingen, Tübingen, Germany

    F Grünebach, U Bross-Bach, L Kanz & P Brossart

Authors
  1. F Grünebach
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. U Bross-Bach
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L Kanz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. P Brossart
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to P Brossart.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Grünebach, F., Bross-Bach, U., Kanz, L. et al. Detection of a new JAK2 D620E mutation in addition to V617F in a patient with polycythemia vera. Leukemia 20, 2210–2211 (2006). https://doi.org/10.1038/sj.leu.2404419

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.leu.2404419

This article is cited by

Search

Advanced search

Quick links