Acquired cooperative CSF3R and RUNX1 mutations in approximately 55% of CN/AML patients are a unique feature and may reflect the inherited background of patients with CN-associated gene mutations, such as those in ELANE or HAX1. Mechanistically, ELANE mutations induce unfolded protein response (UPR) [28, 29] and endoplasmic reticulum (ER) stress, while mutations in HAX1 have pro-apoptotic functions [30, 31]. Here, ELANE is linked to cyclic hematopoiesis.