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:

Analysis of calreticulin mutations in Chinese patients with essential thrombocythemia: clinical implications in diagnosis, prognosis and treatment

Leukemia volume 28, pages 1912–1914 (2014)Cite this article

Subjects

The somatic mutation JAK2 V617F is considered to be one of the most notable landmarks in the diagnosis of classic Philadelphia-chromosome-negative myeloproliferative neoplasms (MPNs). About 50% of patients with essential thrombocythemia (ET) or primary myelofibrosis (PMF) do not harbor JAK2 V617F mutation, and among these patients up to 10% have MPL exon 10 mutations.1, 2, 3, 4 Recently, the discovery of mutations in calreticulin (CALR), with a mutational frequency of 49–71% in JAK2 V617F-negative ET, has filled the molecular diagnostic gap for MPN.1, 2, 3, 4, 5, 6, 7, 8, 9, 10 However, the prevalence of CALR mutations has not been reported in Asian patients, and its therapeutic implications have not yet been evaluated. Here, we explored the utility of CALR mutations in the diagnosis, prognosis and treatment of ET in Chinese patients and provided additional details about the effect of cytoreductive therapy on CALR-mutated clones.

We enrolled 436 ET patients diagnosed according to the 2008 World Health Organization criteria.11 Their clinical records were reassessed, and bone marrow biopsies were carefully reviewed to exclude prefibrotic myelofibrosis. Real-time quantitative PCR assay was performed to detect JAK2 V617F mutation. Mutations in CALR exon 9 and MPL exon 10 were assessed by bidirectional sequencing in ET patients and in 159 healthy controls. Detailed methods are available in the Supplementary Material.

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. Klampfl T, Gisslinger H, Harutyunyan AS, Nivarthi H, Rumi E, Milosevic JD et al. Somatic mutations of calreticulin in myeloproliferative neoplasms. N Engl J Med 2013; 369: 2379–2390.

    Article  CAS  Google Scholar 

  2. Nangalia J, Massie CE, Baxter EJ, Nice FL, Gundem G, Wedge DC et al. Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. N Engl J Med 2013; 369: 2391–2405.

    Article  CAS  Google Scholar 

  3. Rumi E, Pietra D, Ferretti V, Klampfl T, Harutyunyan AS, Milosevic JD et al. JAK2 or CALR mutation status defines subtypes of essential thrombocythemia with substantially different clinical course and outcomes. Blood 2013; 123: 1544–1551.

    Article  Google Scholar 

  4. Rotunno G, Mannarelli C, Guglielmelli P, Pacilli A, Pancrazzi A, Pieri L et al. Impact of Calreticulin mutations on clinical and hematological phenotype and outcome in essential thrombocythemia. Blood 2013; 123: 1552–1555.

    Article  Google Scholar 

  5. Lundberg P, Karow A, Nienhold R, Looser R, Hao-Shen H, Nissen I et al. Clonal evolution and clinical correlates of somatic mutations in myeloproliferative neoplasms. Blood 2014; 123: 2220–2228.

    Article  CAS  Google Scholar 

  6. Tefferi A, Pardanani A . Genetics: CALR mutations and a new diagnostic algorithm for MPN. Nat Rev Clin Oncol 2014; 11: 125–126.

    Article  CAS  Google Scholar 

  7. Tefferi A, Guglielmelli P, Lasho TL, Rotunno G, Finke C, Mannarelli C et al. CALR and ASXL1 mutations-based molecular prognostication in primary myelofibrosis: an international study of 570 patients. Leukemia 2014; e-pub ahead of print 5 February 2014; doi:10.1038/leu.2014.57.

    Article  CAS  Google Scholar 

  8. Guglielmelli P, Nangalia J, Green AR, Vannucchi AM . CALR mutations in myeloproliferative neoplasms: Hidden behind the reticulum. Am J Hematol 2014; 89: 453–456.

    Article  CAS  Google Scholar 

  9. Tefferi A, Lasho TL, Finke CM, Knudson RA, Ketterling R, Hanson CH et al. CALR vs JAK2 vs MPL-mutated or triple-negative myelofibrosis: clinical, cytogenetic and molecular comparisons. Leukemia 2014; e-pub ahead of print 9 January 2014; doi:10.1038/leu.2014.3.

    Article  CAS  Google Scholar 

  10. Tefferi A, Lasho TL, Finke C, Belachew AA, Wassie EA, Ketterling RP et al. Type 1 vs type 2 calreticulin mutations in primary myelofibrosis: differences in phenotype and prognostic impact. Leukemia 2014; e-pub ahead of print 26 February 2014; doi:10.1038/leu.2014.83.

    Article  CAS  Google Scholar 

  11. Tefferi A, Vardiman JW . Classification and diagnosis of myeloproliferative neoplasms: the 2008 World Health Organization criteria and point-of-care diagnostic algorithms. Leukemia 2008; 22: 14–22.

    Article  CAS  Google Scholar 

  12. Green MR, Gentles AJ, Nair RV, Irish JM, Kihira S, Liu CL et al. Hierarchy in somatic mutations arising during genomic evolution and progression of follicular lymphoma. Blood 2013; 121: 1604–1611.

    Article  CAS  Google Scholar 

  13. Lasho TL, Elliott MA, Pardanani A, Tefferi A . CALR mutation studies in chronic neutrophilic leukemia. Am J Hematol 2014; 89: 450.

    Article  CAS  Google Scholar 

  14. Vannucchi AM, Rotunno G, Bartalucci N, Raugei G, Carrai V, Balliu M et al. Calreticulin mutation-specific immunostaining in myeloproliferative neoplasms: pathogenetic insight and diagnostic value. Leukemia 2014; e-pub ahead of print 12 March 2014; doi:10.1038/leu.2014.100.

    Article  CAS  Google Scholar 

  15. Barbui T, Finazzi G, Carobbio A, Thiele J, Passamonti F, Rumi E et al. Development and validation of an International Prognostic Score of thrombosis in World Health Organization-essential thrombocythemia (IPSET-thrombosis). Blood 2012; 120: 5128–5133.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by 863 projects of Ministry of Science and Technology of China (2012AA02A211 and 2011ZX09302-007-04), National Natural Science Foundation of China (81270595), National Public Health Grand Research Foundation (No.201202017), Young Fund of Peking Union Medical College (2013) and Tianjin Municipal Science and Technology Commission (11JCZDJC18600 and 13JCZDJC31200).

Author information

Authors and Affiliations

  1. Thrombosis and Hemostasis Center, State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China

    R Fu, M Xuan, Y Zhou, T Sun, J Bai, Z Cao, L Zhang, H Li, D Zhang, X Zhang, C Lv, F Xue, X Liu, R Yang & L Zhang

Authors
  1. R Fu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M Xuan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Y Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. T Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J Bai
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Z Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. L Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. H Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. D Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. X Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. C Lv
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. F Xue
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. X Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. R Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. L Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to R Yang or L Zhang.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies this paper on the Leukemia website

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fu, R., Xuan, M., Zhou, Y. et al. Analysis of calreticulin mutations in Chinese patients with essential thrombocythemia: clinical implications in diagnosis, prognosis and treatment. Leukemia 28, 1912–1914 (2014). https://doi.org/10.1038/leu.2014.138

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/leu.2014.138

This article is cited by

Search

Advanced search

Quick links