An activating mutation in the CSF3R gene induces a hereditary chronic neutrophilia
(2009) The Journal of Experimental Medicine — Vol. 206, n° 8, p. 1701-1707 (2009)
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- 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.
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Plo, I., Zhang, Y., Le Couedic, J.-P., Nakatake, M., Boulet, J.-M., Itaya, M., Smith, S. O., Debili, N., Constantinescu, S., Vainchenker, W., Louache, F., & de Botton, S. (2009). An activating mutation in the CSF3R gene induces a hereditary chronic neutrophilia. The Journal of Experimental Medicine, 206(8), 1701-1707. https://doi.org/10.1084/jem.20090693 (Original work published 2009)