NUDT15 and leukemia: Pediatric leukemia studies have revealed that patients with this variant can tolerate only 8% of the usual PA dose and account for approximately 22% of PA intolerance cases.[14,15] In vivo and in vitro studies of NUDT15*3 have revealed that this variant does not affect enzyme activity; instead, it causes instability in NUDT15 protein structure, leading to early protein degradation in cells.