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Bioinformatic analyses of CALR mutations in myeloproliferative neoplasms support a role in signaling

Leukemia volume 28, pages 2106–2109 (2014)Cite this article

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Most of JAK2 V617F-negative essential thrombocythemia (ET) and primary myelofibrosis (PMF) patients have mutations in CALR, the gene that encodes calreticulin.1, 2 All CALR mutations were indels located in the last exon of the gene that generate a +1 bp frameshift changing the C-terminal part of the protein. Although several different mutations have been described, two (a 52-bp deletion—type 1 mutation—and a 5-bp insertion—type 2 mutation), account for 80–85% of cases. Type 1 mutation is more frequent in PMF1 and emerging evidence suggests that type 1 and type 2 cases are clinically distinct.3, 4 The pathogenic mechanism of CALR mutations is unclear, but the type 1 mutation induces IL3-independent growth and IL3-hypersensitivity in a Ba/F3 murine model, with an increase in STAT5 phosphorylation.1

CALR is a ubiquitously expressed and evolutionary conserved protein involved in a wide spectrum of important cellular processes. It is mainly located in the endoplasmic reticulum (ER) controlling calcium homeostasis and acting as molecular chaperone, participating in the appropriate folding of several proteins.5, 6 However, other roles outside ER have also been proposed because it has been detected in cytoplasm, nucleus, plasma membrane and in extracellular compartments contributing to different processes such as cell adhesion and gene expression regulation through different signaling pathways.6, 7, 8

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Acknowledgements

This study was supported by a grant from the Research Plan of the University of Navarra (PIUNA Projects).

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Authors and Affiliations

  1. Department of Biochemistry & Genetics, School of Science, University of Navarra, Pamplona, Spain

    L Eder-Azanza, D Navarro, P Aranaz, F J Novo & J L Vizmanos

  2. Wessex Regional Genetics Laboratory, Salisbury NHS Foundation Trust, Salisbury District Hospital, Salisbury, UK

    N C P Cross

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

    N C P Cross

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  1. L Eder-Azanza
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Correspondence to J L Vizmanos.

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Eder-Azanza, L., Navarro, D., Aranaz, P. et al. Bioinformatic analyses of CALR mutations in myeloproliferative neoplasms support a role in signaling. Leukemia 28, 2106–2109 (2014). https://doi.org/10.1038/leu.2014.190

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