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Functional interaction between mutations in the granulocyte colony-stimulating factor receptor in severe congenital neutropenia
journal contribution
posted on 2008-08-01, 00:00 authored by Alister WardAlister Ward, J Gits, F Majeed, A Aprikyan, Rowena Lord, L O`Sullivan, M Freedman, Sarah ShigdarSarah Shigdar, I Touw, D Dale, Y DrorMost 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.