{"doi":"10.1016/j.celrep.2024.113704","title":"Malignant A-to-I RNA editing by ADAR1 drives T cell acute lymphoblastic leukemia relapse via attenuating dsRNA sensing","abstract":"Leukemia-initiating cells (LICs) are regarded as the origin of leukemia relapse and therapeutic resistance. Identifying direct stemness determinants that fuel LIC self-renewal is critical for developing targeted approaches. Here, we show that the RNA-editing enzyme ADAR1 is a crucial stemness factor that promotes LIC self-renewal by attenuating aberrant double-stranded RNA (dsRNA) sensing. Elevated adenosine-to-inosine editing is a common attribute of relapsed T cell acute lymphoblastic leukemia (T-ALL) regardless of molecular subtype. Consequently, knockdown of ADAR1 severely inhibits LIC self-renewal capacity and prolongs survival in T-ALL patient-derived xenograft models. Mechanistically, ADAR1 directs hyper-editing of immunogenic dsRNA to avoid detection by the innate immune sensor melanoma differentiation-associated protein 5 (MDA5). Moreover, we uncover that the cell-intrinsic level of MDA5 dictates the dependency on the ADAR1-MDA5 axis in T-ALL. Collectively, our results show that ADAR1 functions as a self-renewal factor that limits the sensing of endogenous dsRNA. Thus, targeting ADAR1 presents an effective therapeutic strategy for eliminating T-ALL LICs.","journal":"Cell Reports","year":2024,"id":421017,"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":31,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9521,"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":539624,"name":"Haoran Zhang","orcid":"0000-0002-7059-572X","position":1,"is_corresponding":false},{"id":666848,"name":"Jessica Pham","orcid":"0000-0002-4837-6379","position":2,"is_corresponding":false},{"id":667407,"name":"Jane Isquith","orcid":null,"position":3,"is_corresponding":false},{"id":1213885,"name":"Qingchen Jenny Zhou","orcid":null,"position":4,"is_corresponding":false},{"id":1025029,"name":"Larisa Balaian","orcid":null,"position":5,"is_corresponding":false},{"id":469073,"name":"Roman Šášik","orcid":"0000-0002-9266-8993","position":6,"is_corresponding":false},{"id":1213886,"name":"Sabina Enlund","orcid":null,"position":7,"is_corresponding":false},{"id":398125,"name":"Adam Mark","orcid":"0000-0003-4037-9572","position":8,"is_corresponding":false},{"id":666849,"name":"Wenxue Ma","orcid":"0000-0001-9228-6162","position":9,"is_corresponding":false},{"id":666845,"name":"Frida Holm","orcid":"0000-0003-1488-6562","position":10,"is_corresponding":false},{"id":12597,"name":"Kathleen M. Fisch","orcid":"0000-0002-0117-7444","position":11,"is_corresponding":false},{"id":235233,"name":"Dennis John Kuo","orcid":"0000-0003-4154-0057","position":12,"is_corresponding":false},{"id":477605,"name":"Catriona Jamieson","orcid":"0000-0001-8057-6613","position":13,"is_corresponding":false},{"id":103666,"name":"Sara Brin Rosenthal","orcid":"0000-0002-9072-8032","position":14,"is_corresponding":false},{"id":800890,"name":"Maria Rivera","orcid":"0009-0003-9671-0938","position":0,"is_corresponding":true}],"reference_count":95,"raw_metadata":null,"created_at":"2026-07-19T01:57:36.298171Z","pmid":"38265938","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":[]}