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.

Common mutations occurred in our SDS patients who develop AML, and thus, AML is not confined to a rare genetic subgroup of SDS. Newly diagnosed patients with AML are unlikely to have an underlying undiagnosed SDS. Acquired SBDS gene mutations also would appear unlikely to play a mechanistic role in de novo AML, and might not be involved in the pathogenesis of chromosome 7 abnormalities as well.