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Thromb Haemost 2018; 118(09): 1586-1599
DOI: 10.1055/s-0038-1667015
Endothelium and Angiogenesis
Georg Thieme Verlag KG Stuttgart · New York

Endothelial Cells Harbouring the JAK2V617F Mutation Display Pro-Adherent and Pro-Thrombotic Features

Anna Guadall   *
1   INSERM, UMRS_1131, Institut Universitaire d'Hématologie, Université Paris-Diderot, Hopital Saint-Louis, Paris, France
,
Elodie Lesteven   *
1   INSERM, UMRS_1131, Institut Universitaire d'Hématologie, Université Paris-Diderot, Hopital Saint-Louis, Paris, France
,
Gil Letort
1   INSERM, UMRS_1131, Institut Universitaire d'Hématologie, Université Paris-Diderot, Hopital Saint-Louis, Paris, France
,
Sarah Awan Toor
1   INSERM, UMRS_1131, Institut Universitaire d'Hématologie, Université Paris-Diderot, Hopital Saint-Louis, Paris, France
,
Marc Delord
2   Bioinformatique, Institut Universitaire d'Hématologie, Université Paris-Diderot, Hopital Saint-Louis, Paris, France
,
Doriane Pognant
1   INSERM, UMRS_1131, Institut Universitaire d'Hématologie, Université Paris-Diderot, Hopital Saint-Louis, Paris, France
,
Mégane Brusson
3   INSERM, INTS, Unité Biologie Intégrée du Globule Rouge, Paris, France
,
Emmanuelle Verger
1   INSERM, UMRS_1131, Institut Universitaire d'Hématologie, Université Paris-Diderot, Hopital Saint-Louis, Paris, France
4   APHP, Laboratoire de Biologie Cellulaire, Hopital Saint-Louis, Paris, France
,
Nabih Maslah
1   INSERM, UMRS_1131, Institut Universitaire d'Hématologie, Université Paris-Diderot, Hopital Saint-Louis, Paris, France
4   APHP, Laboratoire de Biologie Cellulaire, Hopital Saint-Louis, Paris, France
,
Stéphane Giraudier
1   INSERM, UMRS_1131, Institut Universitaire d'Hématologie, Université Paris-Diderot, Hopital Saint-Louis, Paris, France
4   APHP, Laboratoire de Biologie Cellulaire, Hopital Saint-Louis, Paris, France
5   Universite Paris Diderot, Paris, France
,
Jerome Larghero
6   APHP, Laboratoire de Therapie Cellulaire, Hopital Saint-Louis, Paris, France
,
Valerie Vanneaux
6   APHP, Laboratoire de Therapie Cellulaire, Hopital Saint-Louis, Paris, France
,
Christine Chomienne
1   INSERM, UMRS_1131, Institut Universitaire d'Hématologie, Université Paris-Diderot, Hopital Saint-Louis, Paris, France
4   APHP, Laboratoire de Biologie Cellulaire, Hopital Saint-Louis, Paris, France
5   Universite Paris Diderot, Paris, France
,
Wassim El Nemer
3   INSERM, INTS, Unité Biologie Intégrée du Globule Rouge, Paris, France
,
Bruno Cassinat
1   INSERM, UMRS_1131, Institut Universitaire d'Hématologie, Université Paris-Diderot, Hopital Saint-Louis, Paris, France
4   APHP, Laboratoire de Biologie Cellulaire, Hopital Saint-Louis, Paris, France
,
Jean-Jacques Kiladjian   **
1   INSERM, UMRS_1131, Institut Universitaire d'Hématologie, Université Paris-Diderot, Hopital Saint-Louis, Paris, France
5   Universite Paris Diderot, Paris, France
7   APHP, Centre d'Investigations Cliniques, Hopital Saint-Louis, Paris, France
› Author Affiliations Funding This work has been supported by grants from INCa (PLBio), Lilly Research Programs and Novartis.
Further Information

Publication History

18 April 2018

06 June 2018

Publication Date:
13 August 2018 (online)

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Abstract

Thromboembolic events are the main cause of mortality in BCR-ABL1-negative myeloproliferative neoplasms (MPNs) but their underlying mechanisms are largely unrecognized. The Janus kinase 2 (JAK2)V617F mutation is the most frequent genetic alteration leading to MPN. Usually found in haematopoietic progenitors and stem cells, this mutation has also been described in endothelial cells (ECs) of MPN patients. In this study, we have questioned the impact of the JAK2V617F mutation on EC phenotype and functions. We developed an induced pluripotent stem cells strategy to compare JAK2 mutant and wild-type ECs. Transcriptomic assays showed that several genes and pathways involved in inflammation, cell adhesion and thrombotic events were over-represented in JAK2V617F ECs and expression levels of von Willebrand factor and P-selectin (CD62P) proteins were increased. Finally, we found that leucocytes from MPN patients adhere more tightly to JAK2V617F ECs. Our results show that JAK2V617F ECs have a pro-inflammatory and pro-thrombotic phenotype and were functionally pro-adherent.

Keywords

BCR-ABL1-negative myeloproliferative neoplasms - JAK2V617F mutation - thrombosis - endothelial cells - induced pluripotent stem cells

* These authors contributed equally to this work.


** Jean-Jacques Kiladjian co-supervised the study.


Supplementary Material

 

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