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Functional interaction between mutations in the granulocyte colony-stimulating factor receptor in severe congenital neutropenia

Version 2 2024-06-06, 10:37
Version 1 2014-10-28, 08:36
journal contribution
posted on 2024-06-06, 10:37 authored by Alister WardAlister Ward, J Gits, F Majeed, AA Aprikyan, RS Lewis, LA O'Sullivan, M Freedman, Sarah ShigdarSarah Shigdar, IP Touw, DC Dale, Y Dror
SummaryMost severe congenital neutropenia (SCN) cases possess constitutive neutrophil elastase mutations; a smaller cohort has acquired mutations truncating the granulocyte colony‐stimulating factor receptor (G‐CSF‐R). We have described a case with constitutive extracellular G‐CSF‐R mutation hyporesponsive to ligand. Here we report two independent acquired G‐CSF‐R truncation mutations and a novel constitutive neutrophil elastase mutation in this patient. Co‐expression of a truncated receptor chain restored STAT5 signalling responses of the extracellular G‐CSF‐R mutant, while constitutively‐active STAT5 enhanced its proliferative capacity. These data add to our knowledge of SCN and further highlight the importance of STAT5 in mediating proliferative responses to G‐CSF.

History

Journal

British Journal of Haematology

Volume

142

Pagination

653-656

Location

England

ISSN

0007-1048

eISSN

1365-2141

Language

English

Notes

Published Online: 30 May 2008

Publication classification

C1 Refereed article in a scholarly journal

Copyright notice

2008, The Authors

Issue

4

Publisher

WILEY-BLACKWELL