Your browser doesn't support javascript.
loading
SOD1 is a synthetic lethal target in PPM1D-mutant leukemia cells.
Zhang, Linda; Hsu, Joanne I; Braekeleer, Etienne D; Chen, Chun-Wei; Patel, Tajhal D; Martell, Alejandra G; Guzman, Anna G; Wohlan, Katharina; Waldvogel, Sarah M; Urya, Hidetaka; Tovy, Ayala; Callen, Elsa; Murdaugh, Rebecca; Richard, Rosemary; Jansen, Sandra; Vissers, Lisenka; de Vries, Bert B A; Nussenzweig, Andre; Huang, Shixia; Coarfa, Cristian; Anastas, Jamie N; Takahashi, Koichi; Vassiliou, George; Goodell, Margaret A.
Affiliation
  • Zhang L; Translational Biology and Molecular Medicine Graduate Program, Baylor College of Medicine, Houston, TX.
  • Hsu JI; Medical Scientist Training Program, Baylor College of Medicine, Houston, TX.
  • Braekeleer ED; Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston TX.
  • Chen CW; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX.
  • Patel TD; Center for Cell and Gene Therapy, Houston, TX.
  • Martell AG; Translational Biology and Molecular Medicine Graduate Program, Baylor College of Medicine, Houston, TX.
  • Guzman AG; Medical Scientist Training Program, Baylor College of Medicine, Houston, TX.
  • Wohlan K; Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston TX.
  • Waldvogel SM; Department of Haematology, Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge.
  • Urya H; Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston TX.
  • Tovy A; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX.
  • Callen E; Center for Cell and Gene Therapy, Houston, TX.
  • Murdaugh R; Integrated Molecular and Biomedical Sciences Graduate Program, Baylor College of Medicine, Houston, TX.
  • Richard R; Texas Children's Hospital Department of Hematology/Oncology, Baylor College of Medicine, Houston, TX.
  • Jansen S; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX.
  • Vissers L; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX.
  • de Vries BBA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX.
  • Nussenzweig A; Medical Scientist Training Program, Baylor College of Medicine, Houston, TX.
  • Huang S; Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston TX.
  • Coarfa C; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX.
  • Anastas JN; Center for Cell and Gene Therapy, Houston, TX.
  • Takahashi K; Cancer and Cell Biology Graduate Program, Baylor College of Medicine, Houston, TX.
  • Vassiliou G; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
  • Goodell MA; Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston TX.
bioRxiv ; 2024 Jan 17.
Article in En | MEDLINE | ID: mdl-37693622
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 pharmacologic 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 the protective role of SOD1 against oxidative stress in PPM1D-mutant leukemia cells and highlight a new potential therapeutic strategy against PPM1D-mutant cancers.

Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: BioRxiv Year: 2024 Document type: Article Country of publication:

Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: BioRxiv Year: 2024 Document type: Article Country of publication: