CALR-ETdb, the database of calreticulin variants diversity in essential thrombocythemia

Abstract

Essential thrombocythemia (ET) is a blood cancer defined by a strong increase of platelet numbers. A quarter of patients suffering from ET show mutations in the last exon of calreticulin (CALR) gene. Two variants named type 1 and type 2 represent 85% of these patients. However, a large number of other variants have been determined. In this study, we have compiled variants taken from COSMIC database and literature leading to 155 different variants. This large number of variants allowed redefining 5 new classes extending the classification of type 1-like and type 2-like to a finer description. These analyses showed that last class, named E, corresponding to more than 10% of CALR variants seemed not attached to ET. Structural properties analyzed showed that CALR variants associated to ET have common features. All the compiled and refined information had been included into a freely dedicated database CALR-ETdb (https://www.dsimb.inserm.fr/CALR-ET).

Graphical Abstract

Keywords:

• Classification
• database
• MPN
• protein structural models
• sequence analyses

Acknowledgements

This work was supported by grants from the Ministry of Research (France), University of Paris (formerly University Paris Diderot, Sorbonne, Paris Cité, France), National Institute for Blood Transfusion (INTS, France), National Institute for Health and Medical Research (INSERM, France), and labex GR-Ex. AdB acknowledges the Indo-French Centre for the Promotion of Advanced Research/CEFIPRA for collaborative grants (numbers 5302-2). AdB acknowledges the French National Research Agency with grant ANR-19-CE17-0021 (BASIN). This study was supported by grants from the Laboratory of Excellence GR-Ex, reference ANR-11-LABX-0051. The labex GR-Ex is funded by the programme “Investissements d’avenir” of the French National Research Agency, reference ANR-11-IDEX-0005-02. Calculations were performed on an SGI cluster granted by Conseil Régional Ile de France and INTS (SESAME Grant). The author was granted access to high performance computing (HPC) resources at the French National Computing Centre CINES under grants no. A0070710961
funded by the GENCI (Grand Equipement National de Calcul Intensif).

The funding bodies have no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.

Disclosure Statement

The authors have no conflict of interest to declare.

Author Contribution

AdB designed the study, supervised all the steps of the different part of the study, wrote the original draft and finalized it. NEJ had done all the curation of the sequences, performed sequence and structure analyses and predictions, proposed the new classification, created the database and was involved final draft of the manuscript. GC helped in the database development and was involved final draft of the manuscript.

Additional information

Funding

This work was supported by the Agence Nationale de la Recherche [ANR-11-IDEX-0005-02,ANR-11-LABX-0051,ANR-19-CE17-0021]; Indo-French Centre for the Promotion of Advanced Research [5302-2]; Grand Equipement National de Calcul Intensif [A0070710961].