{"doi":"10.7554/elife.91611.2.sa4","title":"Author Response: SOD1 is a synthetic lethal target in PPM1D-mutant leukemia cells","abstract":"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.","journal":null,"year":2024,"id":496256,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9549,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":845936,"name":"Joanne I. Hsu","orcid":"0000-0002-1194-0650","position":1,"is_corresponding":false},{"id":1158751,"name":"Étienne De Braekeleer","orcid":"0000-0003-4659-023X","position":2,"is_corresponding":false},{"id":1158752,"name":"Chun-Wei Chen","orcid":"0000-0001-6761-3002","position":3,"is_corresponding":false},{"id":708067,"name":"Tajhal D. Patel","orcid":null,"position":4,"is_corresponding":false},{"id":1159288,"name":"Alejandra G. Martell","orcid":null,"position":5,"is_corresponding":false},{"id":377781,"name":"Anna Guzman","orcid":null,"position":6,"is_corresponding":false},{"id":1033361,"name":"Katharina Wohlan","orcid":"0000-0002-9147-4070","position":7,"is_corresponding":false},{"id":1158753,"name":"Sarah M. Waldvogel","orcid":"0000-0002-3657-1951","position":8,"is_corresponding":false},{"id":1173111,"name":"Hidetaka Urya","orcid":null,"position":9,"is_corresponding":false},{"id":483500,"name":"Ayala Tovy","orcid":"0000-0002-3621-6642","position":10,"is_corresponding":false},{"id":246622,"name":"Elsa Callén","orcid":"0000-0002-6325-0221","position":11,"is_corresponding":false},{"id":663640,"name":"Rebecca Murdaugh","orcid":"0000-0002-9950-8634","position":12,"is_corresponding":false},{"id":1159289,"name":"Rosemary Richard","orcid":null,"position":13,"is_corresponding":false},{"id":717913,"name":"Sandra Jansen","orcid":"0000-0001-9453-8124","position":14,"is_corresponding":false},{"id":633062,"name":"Lisenka E.L.M. Vissers","orcid":"0000-0001-6470-5497","position":15,"is_corresponding":false},{"id":1172786,"name":"Bert de Vries","orcid":"0000-0002-2789-2120","position":16,"is_corresponding":false},{"id":248586,"name":"André Nussenzweig","orcid":null,"position":17,"is_corresponding":false},{"id":2210,"name":"Shixia Huang","orcid":"0000-0003-2878-4129","position":18,"is_corresponding":false},{"id":63736,"name":"Cristian Coarfa","orcid":"0000-0002-4183-4939","position":19,"is_corresponding":false},{"id":478864,"name":"Jamie N. Anastas","orcid":"0000-0002-5317-5352","position":20,"is_corresponding":false},{"id":108815,"name":"Koichi Takahashi","orcid":"0000-0002-8027-9659","position":21,"is_corresponding":false},{"id":236906,"name":"George S. Vassiliou","orcid":"0000-0003-4337-8022","position":22,"is_corresponding":false},{"id":284760,"name":"Margaret A. Goodell","orcid":"0000-0003-1111-2932","position":23,"is_corresponding":false},{"id":845938,"name":"Linda Zhang","orcid":"0000-0002-5777-2357","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:09:23.333150Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}