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Functional interaction between mutations in the granulocyte colony‐stimulating factor receptor in severe congenital neutropenia
Author(s) -
Ward Alister C.,
Gits Judith,
Majeed Fidel,
Aprikyan Andrew A.,
Lewis Rowena S.,
O’Sullivan Lynda A.,
Freedman Melvin,
Shigdar Sarah,
Touw Ivo P.,
Dale David C.,
Dror Yigal
Publication year - 2008
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2008.07224.x
Subject(s) - congenital neutropenia , neutrophil extracellular traps , granulocyte colony stimulating factor , neutropenia , mutation , granulocyte , granulocyte colony stimulating factor receptor , neutrophil elastase , elastase , extracellular , immunology , cancer research , biology , medicine , genetics , gene , chemotherapy , biochemistry , inflammation , enzyme
Summary 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.