Recently, Moloney et al. found that in AML cells, the PI3K/AKT, STAT5, and ERK1/2 downstream pathways of FLT3-ITD can promote ROS generation through NOX4D (NOX4 28 kDa splice variant) localized at the nuclear membrane, and inhibiting these pathways could lead to a reduction in ROS production [40], suggesting that NOX4D localized at the nuclear membrane is the main source of pro-survival ROS production and is also a key factor leading to genomic instability and DNA damage [40]. Here, MAPK3 is linked to acute myeloid leukemia.