An activating mutation in the CSF3R gene induces a hereditary chronic neutrophilia.
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Plo I, Zhang Y, Le Couedic JP, Nakatake M, Boulet JM, Itaya M, Smith SO, Debili N, Constantinescu SN, Vainchenker W, Louache F, de Botton S
An activating mutation in the CSF3R gene induces a hereditary chronic neutrophilia.
J Exp Med. 2009 Aug 3;206(8):1701-7. doi: 10.1084/jem.20090693. Epub 2009 Jul 20.
- PubMed ID
- 19620628 [ View in PubMed]
- Abstract
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.