Skip to main content

Thank you for visiting 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.

Pathologic activation of thrombopoietin receptor and JAK2-STAT5 pathway by frameshift mutants of mouse calreticulin

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Prices vary by article type



Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2


  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. Chachoua I, Pecquet C, El-Khoury M, Nivarthi H, Albu RI, Marty C et al. Thrombopoietin receptor activation by myeloproliferative neoplasm associated calreticulin mutants. Blood 2015; e-pub ahead of print 14 December 2015; doi:10.1182/blood-2015-11-681932.

    Article  Google Scholar 

  4. Marty C, Pecquet C, Nivarthi H, Elkhoury M, Chachoua I, Tulliez M et al. Calreticulin mutants in mice induce an MPL-dependent thrombocytosis with frequent progression to myelofibrosis. Blood 2015; e-pub ahead of print 25 November 2015; doi:10.1182/blood-2015-11-679571.

    Article  Google Scholar 

  5. Michalak M, Corbett EF, Mesaeli N, Nakamura K, Opas M . Calreticulin: one protein, one gene, many functions. Biochem J 1999; 344: 281–292.

    Article  CAS  Google Scholar 

  6. Kollmann K, Nangalia J, Warsch W, Quentmeier H, Bench A, Boyd E et al. MARIMO cells harbor a CALR mutation but are not dependent on JAK2/STAT5 signaling. Leukemia 2015; 29: 494–497.

    Article  CAS  Google Scholar 

  7. Yoshida H, Kondo M, Ichihashi T, Hashimoto N, Inazawa J, Ohno R et al. A novel myeloid cell line, Marimo, derived from therapy-related acute myeloid leukemia during treatment of essential thrombocythemia: consistent chromosomal abnormalities and temporary C-MYC gene amplification. Cancer Genet Cytogenet 1998; 100: 21–24.

    Article  CAS  Google Scholar 

  8. Staerk J, Defour JP, Pecquet C, Leroy E, Antoine-Poirel H, Brett I et al. Orientation-specific signalling by thrombopoietin receptor dimers. EMBO J 2011; 30: 4398–4413.

    Article  CAS  Google Scholar 

  9. Kohlhuber F, Rogers NC, Watling D, Feng J, Guschin D, Briscoe J et al. A JAK1/JAK2 chimera can sustain alpha and gamma interferon responses. Mol Cell Biol 1997; 17: 695–706.

    Article  CAS  Google Scholar 

  10. Cong L, Ran FA, Cox D, Lin S, Barretto R, Habib N et al. Multiplex genome engineering using CRISPR/Cas systems. Science 2013; 339: 819–823.

    Article  CAS  Google Scholar 

  11. Mashiko D, Fujihara Y, Satouh Y, Miyata H, Isotani A, Ikawa M . Generation of mutant mice by pronuclear injection of circular plasmid expressing Cas9 and single guided RNA. Sci Rep 2013; 3: 3355.

    Article  Google Scholar 

  12. Passamonti F, Caramazza D, Maffioli M . JAK inhibitor in CALR-mutant myelofibrosis. N Engl J Med 2014; 370: 1168–1169.

    Article  CAS  Google Scholar 

  13. Guglielmelli P, Bartalucci N, Rotunno G, Vannucchi AM . Calreticulin: a new horizon for the testing and treatment of myeloproliferative neoplasms. Expert Rev Hematol 2014; 7: 423–425.

    Article  CAS  Google Scholar 

  14. Nivarthi H, Chen D, Cleary C, Kubesova B, Bogner E, Vainchenker W et al. Thrombopoietin receptor is required for the oncogenic function of CALR mutants. Leukemia 2016; 30: 1759–1763.

    Article  CAS  Google Scholar 

  15. 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 2014; 123: 1544–1551.

    Article  CAS  Google Scholar 

Download references


We thank Dr Patrick Jacquemin for the support with CRISPR/Cas9 approach and Dr Nicolas Dauguet for expert cell sorting. IP is supported by Institut National du Cancer (PLBIO2015); Agence Nationale de la Recherche; (ANR-13-JVSV1-GERMPN-01, I.P.) and Institut National de la Santé et de la Recherche Médicale, Genetics of Hematological Disorders (Inserm). IP, WV and CM are supported by a grant form la Ligue Nationale contre le Cancer (HR 2013, 2016). Support to SNC was from the Ludwig Institute for Cancer Research, FRS-FNRS, Salus Sanguinis Foundation, the Action de Recherche Concertée project ARC10/15–027 of the Université catholique de Louvain, the Fondation contre le Cancer, the PAI Programs BCHM61B5 and Belgian Medical Genetics Initiative. Support from Télévie (IC and TB), FSR (TB) and FRS-FNRS (CP) is acknowledged. HN and RK acknowledge the support received by Austrian Science Fund (FWF: project numbers- F2812-B20 and F4702-B20).

Author information

Authors and Affiliations


Corresponding author

Correspondence to S N Constantinescu.

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

Balligand, T., Achouri, Y., Pecquet, C. et al. Pathologic activation of thrombopoietin receptor and JAK2-STAT5 pathway by frameshift mutants of mouse calreticulin. Leukemia 30, 1775–1778 (2016).

Download citation

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


Quick links