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:

Frequency and clinical correlates of JAK2 46/1 (GGCC) haplotype in primary myelofibrosis

Leukemia volume 24, pages 1533–1537 (2010)Cite this article

Subjects

About sixty-percent of patients with primary myelofibrosis (PMF) harbor the JAK2V617F mutation while about 8–10% present a mutation at codon 515 in MPL exon 10, W515L/K/A.1 These mutations are shared by the other Philadelphia-chromosome negative myeloproliferative neoplasms (MPNs), which include polycythemia vera (PV), essential thrombocythemia (ET), and refractory anemia with ring sideroblasts and thrombocytosis (RARS-T), and represent a major criteria for MPN diagnosis according to the 2008 WHO classification.2 Presence of a JAK2V617F mutated genotype and/or higher V617F allele burden have been variably associated with hematological and clinical characteristics in patients with PV or ET.3 In case of PMF, a significant association of JAK2V617F mutated status with a more pronounced myeloproliferative phenotype favoring raised hemoglobin level and leukocyte count and larger splenomegaly has been reported, although not universally.3 However, the most relevant finding in two independent studies in PMF patients, was that a low JAK2 allele burden at diagnosis represented a strong surrogate marker associated with shortened survival.4, 5

Overall prognosis in PMF is poorer compared to other classic MPNs. An international prognostic score system (IPSS), which allows to discriminate four categories of patients with significantly different median survival, has been developed recently by the International Working Group for Myelofibrosis Research and Treatment (IWG-MRT).6 However, identification of additional factors associated with prognosis is of considerable importance for driving therapeutic decisions. For example, cytogenetic abnormalities have an IPSS-independent value.7 Furthermore, Tefferi et al.8 recently reported that nullizygosity for the JAK2 46/1 haplotype was associated with inferior survival regardless of IPSS score or V617F allele burden.

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. Vannucchi AM, Guglielmelli P, Tefferi A . Advances in understanding and management of myeloproliferative neoplasms. AC- A Cancer Journal for Clinicians 2009; 59: 171–191.

    Article  Google Scholar 

  2. Tefferi A, Thiele J, Orazi A, Kvasnicka HM, Barbui T, Hanson CA et al. Proposals and rationale for revision of the World Health Organization diagnostic criteria for polycythemia vera, essential thrombocythemia, and primary myelofibrosis: recommendations from an ad hoc international expert panel. Blood 2007; 110: 1092–1097.

    Article  CAS  Google Scholar 

  3. Vannucchi AM, Antonioli E, Guglielmelli P, Pardanani A, Tefferi A . Clinical correlates of JAK2V617F presence or allele burden in myeloproliferative neoplasms: a critical reappraisal. Leukemia 2008; 22: 1299–1307.

    Article  CAS  Google Scholar 

  4. 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 

  5. Guglielmelli P, Barosi G, Specchia G, Rambaldi A, Lo Coco F, Antonioli E et al. Identification of patients with poorer survival in primary myelofibrosis based on the burden of JAK2V617F mutated allele. Blood 2009; 114: 1477–1483.

    Article  CAS  Google Scholar 

  6. Cervantes F, Dupriez B, Pereira A, Passamonti F, Reilly JT, Morra E et al. New prognostic scoring system for primary myelofibrosis based on a study of the International Working Group for Myelofibrosis Research and Treatment. Blood 2009; 113: 2895–2901.

    Article  CAS  Google Scholar 

  7. Hussein K, Pardanani AD, van Dyke DL, Hanson CA, Tefferi A . International Prognostic Scoring System-independent cytogenetic risk categorization in primary myelofibrosis. Blood 2010; 115: 496–499.

    Article  CAS  Google Scholar 

  8. 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 

  9. 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 

  10. 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 

  11. 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 JAK2(V617F)-positive myeloproliferative neoplasms. Nat Genet 2009; 41: 455–459.

    Article  CAS  Google Scholar 

  12. 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 

  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. 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 Mar 19. (Epub ahead of print).

  15. Patnaik MM, Lasho T, Finke C, Gangat N, Caramazza D, Siragusa S et al. MPL mutation effect on JAK2 46/1 haplotype frequency in JAK2V617F-negative myeloproliferative neoplasms. Leukemia 2010; 24: 859–860.

    Article  CAS  Google Scholar 

  16. Pancrazzi A, Guglielmelli P, Ponziani V, Bergamaschi G, Bosi A, Barosi G et al. A sensitive detection method for MPLW515L or MPLW515K mutation in chronic myeloproliferative disorders with locked nucleic acid-modified probes and real-time polymerase chain reaction. J Mol Diagn 2008; 10: 435–441.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by the Ministero della Università e Ricerca (COFIN), Istituto Toscano Tumori, Cassa di Risparmio di Pistoia, and Associazione Italiana per la Ricerca sul Cancro. We thank Prof. Nick Cross for helpful discussion.

Author information

Authors and Affiliations

  1. Dipartimento di Area Critica, Unità Funzionale di Ematologia, Università degli Studi, Firenze, Italy

    P Guglielmelli, F Biamonte, A Spolverini, L Pieri, E Antonioli, A Pancrazzi, A Bosi & A M Vannucchi

  2. Istituto Toscano Tumori, Firenze, Italy

    P Guglielmelli, F Biamonte, A Spolverini, L Pieri, E Antonioli, A Pancrazzi, A Bosi & A M Vannucchi

  3. Unità di Epidemiologia Clinica-Centro per lo Studio della Mielofibrosi, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

    A Isgrò & G Barosi

Authors
  1. P Guglielmelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. F Biamonte
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A Spolverini
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. L Pieri
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A Isgrò
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. E Antonioli
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. A Pancrazzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. A Bosi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. G Barosi
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. A M Vannucchi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A M Vannucchi.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Guglielmelli, P., Biamonte, F., Spolverini, A. et al. Frequency and clinical correlates of JAK2 46/1 (GGCC) haplotype in primary myelofibrosis. Leukemia 24, 1533–1537 (2010). https://doi.org/10.1038/leu.2010.126

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/leu.2010.126

This article is cited by

Search

Advanced search

Quick links