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 allele burden, JAK2 46/1 haplotype and clinical features of Chinese with myeloproliferative neoplasms

Leukemia volume 27, pages 1763–1767 (2013)Cite this article

Subjects

Polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) are clonal myeloproliferative neoplasms (MPNs) with a high frequency of the 1849G>T mutation in JAK2 referred to as JAK2V617F. How this mutation gives rise to different clinical phenotypes with diverse prognoses is unknown. Expression of JAK2V617F in genetically modified mice correlates with disease features.1 Some data in humans support this notion.2, 3, 4 Other mutations, including those in JAK2 exon-12, TET2, MPL, EZH2 and ASXL1 occurs at varying frequency5 in persons with MPNs Whether these mutations correlate with disease phenotype and/or prognosis is unknown.

Another possible explanation for the diversity of MPNs associated with JAK2V617F is the genetic background on which the mutation occurs. One potential relevant factor is the specific constitutional JAK2 haplotype, designated 46/1 or GGCC, which is correlated with JAK2V617F in cases of European descent.6, 7, 8, 9

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. Tiedt R, Hao-Shen H, Sobas MA, Looser R, Dirnhofer S, Schwaller J et al. Ratio of mutant JAK2-V617F to wildtype Jak2 determines the MPD phenotypes in transgenic mice. Blood 2008; 111: 3931–3940.

    Article  CAS  Google Scholar 

  2. Passamonti F, Rumi E, Pietra D, Della Porta MG, Boveri E, Pascutto C et al. Relation between JAK2 (V617F) mutation status, granulocyte activation, and constitutive mobilization of CD34+ cells into peripheral blood in myeloproliferative disorders. Blood 2006; 107: 3676–3682.

    Article  CAS  Google Scholar 

  3. Antonioli E, Guglielmelli P, Poli G, Bogani C, Pancrazzi A, Longo G et al. Influence of JAK2V617F allele burden on phenotype in essential thrombocythemia. Haematologica 2008; 93: 41–48.

    Article  CAS  Google Scholar 

  4. Passamonti F, Rumi E, Pietra D, Elena C, Boveri E, Arcaini L et al. A prospective study of 338 subjects with polycythemia vera: the impact of JAK2 (V617F) allele burden and leukocytosis on fibrotic or leukemic disease transformation and vascular complications. Leukemia 2010; 24: 1574–1579.

    Article  CAS  Google Scholar 

  5. Shih AH, Abdel-Wahab O, Patel JP, Levine RL . The role of mutations in epigenetic regulators in myeloid malignancies. Nat Rev Cancer 2012; 12: 599–612.

    Article  CAS  Google Scholar 

  6. Jones AV, Chase A, Silver RT, Oscier D, Zoi K, Wang YL et al. JAK2 haplotype is a major risk factor for the development of myeloproliferative neoplasms. Nat Genet 2009; 41: 446–449.

    Article  CAS  Google Scholar 

  7. Kilpivaara O, Mukherjee S, Schram AM, Wadleigh M, Mullally A, Ebert BL et al. A germline JAK2 SNP is associated with predisposition to the development of JAK2V617F-positive myeloproliferative neoplasms. Nat Genet 2009; 41: 455–459.

    Article  CAS  Google Scholar 

  8. Olcaydu D, Harutyunyan A, Jager R, Berg T, Gisslinger B, Pabinger I et al. A common JAK2 haplotype confers susceptibility to myeloproliferative neoplasms. Nat Genet 2009; 41: 450–454.

    Article  CAS  Google Scholar 

  9. Jones AV, Campbell PJ, Beer PA, Schnittger S, Vannucchi AM, Zoi K et al. The JAK2 46/1 haplotype predisposes to MPL-mutated myeloproliferative neoplasms. Blood 2010; 115: 4517–4523.

    Article  CAS  Google Scholar 

  10. Xu Z, Gale RP, Zhang Y, Qin T, Chen H, Zhang P et al. Unique features of primary myelofibrosis in Chinese. Blood 2012; 119: 2469–2473.

    Article  CAS  Google Scholar 

  11. Lippert E, Girodon F, Hammond E, Jelinek J, Reading NS, Fehse B et al. Concordance of assays designed for the quantification of JAK2V617F: a multicenter study. Haematologica 2009; 94: 38–45.

    Article  CAS  Google Scholar 

  12. Guglielmelli P, Biamonte F, Spolverini A, Pieri L, Isgrò A, Antonioli E et al. Frequency and clinical correlates of JAK2 46/1 (GGCC) haplotype in primary myelofibrosis. Leukemia 2010; 24: 1533–1537.

    Article  CAS  Google Scholar 

  13. Pardanani A, Lasho TL, Finke CM, Gangat N, Wolanskyj AP, Hanson CA et al. The JAK2 46/1 haplotype confers susceptibility to essential thrombocythemia regardless of JAK2V617F mutational status-clinical correlates in a study of 226 consecutive patients. Leukemia 2010; 24: 110–114.

    Article  CAS  Google Scholar 

  14. Olcaydu D, Skoda RC, Looser R, Li S, Cazzola M, Pietra D et al. The ‘GGCC’ haplotype of JAK2 confers susceptibility to JAK2 exon 12 mutation-positive polycythemia vera. Leukemia 2009; 23: 1924–1926.

    Article  CAS  Google Scholar 

  15. Tefferi A, Lasho TL, Patnaik MM, Finke CM, Hussein K, Hogan WJ et al. JAK2 germline genetic variation affects disease susceptibility in primary myelofibrosis regardless of V617F mutational status: nullizygosity for the JAK2 46/1 haplotype is associated with inferior survival. Leukemia 2010; 24: 105–109.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported in part by National Natural Science Funds (No. 81070403,No. 81270585), Tianjin Key Natural Science Funds (12JCZDJC23900), National Public Health Grand Research Foundation (No.201202017) and National Science and Technology Major Project (2011ZX09302-007-04)(to ZX). NCPC and AVJ were supported by Leukemia and Lymphoma Research (UK) and the Kay Kendall Leukemia Fund. RPG acknowledges support from the NIHR Biomedical Research Center funding scheme.

Author information

Author notes

  1. J Wang, Z Xu and L Liu: These authors contributed equally to this work.

Authors and Affiliations

  1. MDS and MPN Centre, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China

    J Wang, Z Xu, L Liu, T Qin, J Xu, T Zhang, X Sun, Y Zhang & Z Xiao

  2. Division of Experimental Medicine, Department of Medicine, Haematology Section, Imperial College, London, UK

    R P Gale

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

    N C P Cross & A V Jones

  4. Faculty of Medicine, University of Southampton, Southampton, UK

    N C P Cross & A V Jones

  5. Molecular diagnostic laboratory, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China

    X Ai & Q Li

  6. Department of Pathology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China

    P Zhang

  7. Department of Pathology, State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China

    Y Zhang & Z Xiao

Authors
  1. J Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Z Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R P Gale
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. N C P Cross
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A V Jones
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. T Qin
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. X Ai
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. J Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. T Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. X Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Q Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. P Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Y Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Z Xiao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Z Xiao.

Ethics declarations

Competing interests

RPG is a part-time employee of Celgene Corp., Summit, NJ. All other authors declare no conflict of interest.

Additional information

Supplementary Information accompanies the paper on the Leukemia website

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wang, J., Xu, Z., Liu, L. et al. JAK2V617F allele burden, JAK2 46/1 haplotype and clinical features of Chinese with myeloproliferative neoplasms. Leukemia 27, 1763–1767 (2013). https://doi.org/10.1038/leu.2013.21

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/leu.2013.21

This article is cited by

Search

Advanced search

Quick links