A congenital CSF3R mutation in chronic neutropenia reveals a vital role for a cytokine receptor extracellular hinge motif in the response to granulocyte colony-stimulating factor.

Autor: Feyen J; Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Ernst MPT; Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., van der Velden VHJ; Department of Immunology, Erasmus MC, Rotterdam, The Netherlands., Valk PJM; Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Broeders L; Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Touw IP; Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Raaijmakers MHGP; Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
Jazyk: angličtina
Zdroj: Pediatric blood & cancer [Pediatr Blood Cancer] 2023 Apr; Vol. 70 (4), pp. e30039. Date of Electronic Publication: 2022 Oct 31.
DOI: 10.1002/pbc.30039
Abstrakt: We describe a patient with congenital neutropenia (CN) with a homozygous germline mutation in the colony-stimulating factor 3 receptor gene (CSF3R). The patient's bone marrow shows lagging neutrophil development with subtle left shift and unresponsiveness to CSF3 in in vitro colony assays. This patient illustrates that the di-proline hinge motif in the extracellular cytokine receptor homology domain of CSF3R is critical for adequate neutrophil production, but dispensable for in vivo terminal neutrophil maturation. This report underscores that CN patients with inherited CSF3R mutations should be marked as a separate clinical entity, characterized by a failure to respond to CSF3.
(© 2022 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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