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A. Guy et al.
ers of EC activation should be intensively investigated to determine which MPN patients are at high thrombotic risk; (ii) it opens the way to new therapeutic options in MPN, such as hydroxyurea in patients at high risk of thrombosis or with raised levels of markers of endothelial activation, as well as anti-P-selectin antibody instead of or in addition to the standard of care to prevent thrombosis in high-risk MPN patients; and (iii) it provides the proof of concept that an acquired genetic mutation can alter the phenotype of EC, as shown for the pro-thrombotic phe- notype acquired upon expression of the JAK2 mutation. This suggests that other activating mutations in EC could be causal in thrombotic disorders of unknown cause, which account for 50% of recurrent venous thromboses.
Acknowledgments
The authors wish to thank Myriam Petit and Annabel Reynaud and Beatrice Jaspard-Vinassa for their assistance in histology, Beatrice Jaspard-Vinassa for her help with western
blots, Jeremie Teillon for his help in image quantification, Veronique Ollivier for her assistance with in vitro flow experi- ments, Sylvain Grolleau for his help in mice genotyping, Olivier Mansier for his help with the quantitative polymerase chain reac- tion, Jerome Guignard for his help with mice and the vectorology platform for lentiviruses production (Inserm U1035). We are grateful to William Vainchenker (Institut Gustave Roussy, Inserm U1009), Pierre-Emmanuel Rautou (Inserm U970) and Jean- François Viallard (Inserm U1034) for their helpful discussions. We are also grateful to the French Intergroup Myeloproliferative (FIM).
Funding
This study was supported by research grants from ANR- DFG JAKPOT (N° ANR-14-CE35-0022-02), INSERM, The Fondation Bettencourt Schueller and the Aquitaine Region. AG was supported by a research grant from INSERM (Poste Accueil INSERM) and VGL was supported by ANR-DFG JAKPOT.
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