Mechanism of the Elevated UPR in CN Patients but not in CyN Patients Carrying Same ELANE Mutations

In severe congenital neutropenia (CN) patients mutated neutrophil elastase (NE) protein induced unfolded protein response (UPR) leading to elevated apoptosis. However, it is unclear, why UPR was not detected in patients with cyclic neutropenia (CyN) carrying the same ELANE mutations. We investigated the mechanism of UPR (activation of ATF6 and ATF6 target genes (GADD34, CHOP and BiP) in CN patients in comparison to CyN patients and to healthy individuals. We detected significantly elevated levels of ATF6 and BiP in myeloid cells of CN patients, in comparison to CyN patients. We transduced the myeloid cell lines…