%0 Journal Article
%T SOD1 is a synthetic-lethal target in PPM1D-mutant leukemia cells.
%A Zhang L
%A Hsu JI
%A Braekeleer ED
%A Chen CW
%A Patel TD
%A Martell AG
%A Guzman AG
%A Wohlan K
%A Waldvogel SM
%A Uryu H
%A Tovy A
%A Callen E
%A Murdaugh RL
%A Richard R
%A Jansen S
%A Vissers L
%A de Vries BBA
%A Nussenzweig A
%A Huang S
%A Coarfa C
%A Anastas J
%A Takahashi K
%A Vassiliou G
%A Goodell MA
%J Elife
%V 12
%N 0
%D 2024 Jun 18
%M 38896450
%F 8.713
%R 10.7554/eLife.91611
%X The DNA damage response is critical for maintaining genome integrity and is commonly disrupted in the development of cancer. PPM1D (protein phosphatase Mg2+/Mn2+-dependent 1D) is a master negative regulator of the response; gain-of-function mutations and amplifications of PPM1D are found across several human cancers making it a relevant pharmacological target. Here, we used CRISPR/Cas9 screening to identify synthetic-lethal dependencies of PPM1D, uncovering superoxide dismutase-1 (SOD1) as a potential target for PPM1D-mutant cells. We revealed a dysregulated redox landscape characterized by elevated levels of reactive oxygen species and a compromised response to oxidative stress in PPM1D-mutant cells. Altogether, our results demonstrate a role for SOD1 in the survival of PPM1D-mutant leukemia cells and highlight a new potential therapeutic strategy against PPM1D-mutant cancers.