RPN1 and acute myeloid leukemia: Interestingly, it was also shown that RPN1-EVI1 AML cells exhibit enhanced sensitivity to PRMT5 inhibition and likewise overexpression of EVI1 induced the degradation of the ATF4 protein and enhanced ROS, suggesting that PRMT5-mediated regulation of ATF4 is critical to counteract the deleterious oncogenic signaling of EVI1 [48].