RPN1 and acute myeloid leukemia: AML cells have been found to be reliant on ATF4 to regulate survival upon exposure to reactive oxygen species (ROS) as it was shown that in AML cells bearing the inv (3) (RPN1-EVI1) chromosomal rearrangement, pharmacological inhibition of PRMT5, which as described above regulates ATF4 mRNA splicing and stability, led to production of an unstable, intron-retained ATF4 mRNA that was restricted to the nucleus and resulted in reduced ATF4 protein levels and increased ROS [48].