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

AC (Alister) Ward, JHC Gits, F Majeed, AA Aprikyan, RS Lewis, LA O'Sullivan, M Freedman, S Shigdar, Ivo Touw, DC Dale, Y Dror

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10 Citations (Scopus)


Most 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.
Original languageUndefined/Unknown
Pages (from-to)653-656
Number of pages4
JournalBritish Journal of Haematology
Issue number4
Publication statusPublished - 2008

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  • EMC MM-02-41-04

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