Graphical representation of the PML-mediated responses in ELANE-I60F HPCs.ELANE mutations with predicted NE misfolding result in excessive doses of ROS, inducing the formation of PML-NBs. PML-NBs are important for reducing ROS levels, while also inducing metabolism, proliferation, and cell cycling. In addition, PML reduces the response to CSF3 and induces the transcription of (mutant) ELANE, providing a feed-forward mechanism.