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An activating mutation in the CSF3R gene induces a hereditary chronic neutrophilia

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Plo, Isabelle Zhang, Yanyan Le Couedic, Jean-Pierre Nakatake, Mayuka Boulet, Jean-Michel Constantinescu, Stefan N. [UCL] de Botton, Stephane

We identify an autosomal mutation in the CSF3R gene in a family with a chronic neutrophilia. This T617N mutation energetically favors dimerization of the granulocyte colony-stimulating factor (G-CSF) receptor transmembrane domain, and thus, strongly promotes constitutive activation of the receptor and hypersensitivity to G-CSF for proliferation and differentiation, which ultimately leads to chronic neutrophilia. Mutant hematopoietic stem cells yield a myeloproliferative-like disorder in xenotransplantation and syngenic mouse bone marrow engraftment assays. The survey of 12 affected individuals during three generations indicates that only one patient had a myelodysplastic syndrome. Our data thus indicate that mutations in the CSF3R gene can be responsible for hereditary neutrophilia mimicking a myeloproliferative disorder.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès libre
Publication date 2009
Language Anglais
Journal information "The Journal of Experimental Medicine" - Vol. 206, no. 8, p. 1701-1707 (2009)
Peer reviewed yes
Publisher Rockefeller Univ Press (New York)
issn 0022-1007
e-issn 1540-9538
Publication status Publié
Affiliation UCL
Links
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Bibliographic reference Plo, Isabelle ; Zhang, Yanyan ; Le Couedic, Jean-Pierre ; Nakatake, Mayuka ; Boulet, Jean-Michel ; et. al. An activating mutation in the CSF3R gene induces a hereditary chronic neutrophilia. In: The Journal of Experimental Medicine, Vol. 206, no. 8, p. 1701-1707 (2009)
Permanent URL http://hdl.handle.net/2078.1/35422