Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Increased reactive oxygen species production and p47phox phosphorylation in neutrophils from myeloproliferative disorders patients with JAK2 (V617F) mutation
Haematologica, Volume 98, No. 10, Year 2013
Notification
URL copied to clipboard!
Description
Myeloproliferative disorders are associated with increased risk of thrombosis and vascular complications. The pathogenesis of these complications is not completely known. Reactive oxygen species produced by the neutrophil NADPH oxidase could have a role in this process. The aim of this study was to evaluate reactive oxygen species production by neutrophils of myeloproliferative disorder patients. Patients with or without the JAK2 V617F mutation were characterized. Reactive oxygen species production was assessed by chemiluminescence, and phosphorylation of the NADPH oxidase subunit p47phox was analyzed by Western blots. In a comparison of controls and myeloproliferative disorder patients without the JAK2 V617F mutation, reactive oxygen species production by neutrophils from patients with the JAK2 V617F mutation was dramatically increased in non-stimulated and in stimulated conditions. This increase was associated with increased phosphorylation of the p47phox on Ser345 and of the uspstream kinase ERK1/2. In neutrophils from healthy donors, JAK2 can be activated by GM-CSF. GM-CSFinduced p47phox phosphorylation and priming of reactive oxygen species production are inhibited by the selective JAK2 inhibitors AG490 and lestaurtinib (CEP-701), supporting a role for JAK2 in the upregulation of NADPH oxidase activation. These findings show an increase in reactive oxygen species production and p47phox phosphorylation in neutrophils from myeloproliferative disorder patients with the JAK2 V617F mutation, and demonstrate that JAK2 is involved in GM-CSF-induced NADPH oxidase hyperactivation. As neutrophil hyperactivation could be implicated in the thrombophilic status of patients with myeloproliferative disorders, aberrant activation of JAK2 V617F, leading to excessive neutrophil reactive oxygen species production might play a role in this setting. © 2013 Ferrata Storti Foundation.
Authors & Co-Authors
Hurtado-Nédelec, Margarita
France, Paris
Centre de Recherche Biomédicale Bichat-beaujon
France, Paris
Université Paris Cité
France, Paris
Hôpital Bichat-claude-bernard Ap-hp
Csillag, Marie José Grange
France, Paris
Hôpital Bichat-claude-bernard Ap-hp
Boussetta, Tarek
France, Paris
Centre de Recherche Biomédicale Bichat-beaujon
France, Paris
Université Paris Cité
Belambri, Sahra Amel
Algeria, Setif
Université Ferhat Abbas Sétif 1
Fay, Michèle
France, Paris
Centre de Recherche Biomédicale Bichat-beaujon
France, Paris
Université Paris Cité
Cassinat, Bruno
France, Paris
Ap-hp Assistance Publique - Hopitaux de Paris
France, Paris
Hôpital Saint-louis
Gougerot, Marie Anne Pocidalo
France, Paris
Centre de Recherche Biomédicale Bichat-beaujon
France, Paris
Université Paris Cité
France, Paris
Hôpital Bichat-claude-bernard Ap-hp
Dang, Pham My Chan
France, Paris
Centre de Recherche Biomédicale Bichat-beaujon
France, Paris
Université Paris Cité
El-Benna, Jamel
France, Paris
Centre de Recherche Biomédicale Bichat-beaujon
France, Paris
Université Paris Cité
Statistics
Citations: 52
Authors: 9
Affiliations: 6
Identifiers
Doi:
10.3324/haematol.2012.082560
ISSN:
03906078
e-ISSN:
15928721
Research Areas
Cancer