SOD1 is a synthetic lethal target in PPM1D-mutant leukemia cells

Using CRISPR/Cas9 dropout screening, we identified superoxide dismutase-1 (SOD1) as a genetic dependency specific to PPM1D-mutant leukemia cells. We found that the mutant cells exhibited a compromised response to oxidative stress that can be rescued with SOD1 inhibitors. PPM1D-mutant fcells also exhibit significant genomic instability, highlighting the essential role of SOD1 in safeguarding against oxidative stress and DNA damage. Overall design: Transcriptomic profiling of RNA-seq data for WT and PPM1D-mutant Cas9-OCI-AML2 cells with or without SOD1-knockout.