{"doi":"10.1172/jci183761","title":"Jab1 promotes immune evasion and progression in acute myeloid leukemia models under oxidative stress","abstract":"<jats:p>\n                    Acute myeloid leukemia (AML) is the most common hematological malignancy. Leukemia stem cells exhibit high levels of oxidative stress, with ROS being the primary products of this stress, inducing the expression of c-JUN activation domain-binding protein 1 (Jab1). Previous studies have demonstrated that Jab1, as a transcriptional coactivator of c-JUN, promotes the malignant progression of AML under oxidative stress. However, its role in immune evasion is still under investigation. Here, we observed that knocking out Jab1 reduced the expression of immune checkpoints in vivo, effectively overcoming the immune evasion of AML. Interestingly, the deletion of Jab1 had no impact on the maturation of normal hematopoietic cells in mice. Mechanistically, Jab1 directly activated IGF2BP3 by driving the transcription factor c-JUN, consequently modulated the m\n                    <jats:sup>6</jats:sup>\n                    A modification of LILRB4 mRNA, and promoted immune evasion in AML. Finally, CSN5i-3 effectively disrupted the signaling pathway mediated by Jab1, thereby restoring cellular immune surveillance and halting the progression of AML. Thus, our results highlight the functional role of Jab1 in supporting AML survival and support the development of targeted therapeutic strategies.\n                  </jats:p>","journal":"Journal of Clinical Investigation","year":2025,"id":690083,"datarank":0.29188652235829704,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.0,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":453580,"name":"Qian Wang","orcid":"0000-0002-1201-865X","position":1,"is_corresponding":false},{"id":1802842,"name":"Guopeng Chen","orcid":null,"position":2,"is_corresponding":false},{"id":1064426,"name":"Li Liu","orcid":"0000-0001-6126-2635","position":3,"is_corresponding":false},{"id":441532,"name":"Zhiying Wang","orcid":"0000-0002-7226-1686","position":4,"is_corresponding":false},{"id":1802843,"name":"Linlu Ma","orcid":null,"position":5,"is_corresponding":false},{"id":1802844,"name":"Yuxing Liang","orcid":null,"position":6,"is_corresponding":false},{"id":1506598,"name":"Jinxian Wu","orcid":null,"position":7,"is_corresponding":false},{"id":1312482,"name":"Xinqi Li","orcid":"0009-0002-4799-8333","position":8,"is_corresponding":false},{"id":410839,"name":"Xiaoyan Liu","orcid":"0000-0001-8789-5211","position":9,"is_corresponding":false},{"id":1711179,"name":"Fuling Zhou","orcid":null,"position":10,"is_corresponding":false},{"id":1326696,"name":"Nan Zhang","orcid":"0000-0002-5877-1786","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Jab1 promotes immune evasion and progression in acute myeloid leukemia models under oxidative stress","abstract":"<jats:p>\n                    Acute myeloid leukemia (AML) is the most common hematological malignancy. Leukemia stem cells exhibit high levels of oxidative stress, with ROS being the primary products of this stress, inducing the expression of c-JUN activation domain-binding protein 1 (Jab1). Previous studies have demonstrated that Jab1, as a transcriptional coactivator of c-JUN, promotes the malignant progression of AML under oxidative stress. However, its role in immune evasion is still under investigation. Here, we observed that knocking out Jab1 reduced the expression of immune checkpoints in vivo, effectively overcoming the immune evasion of AML. Interestingly, the deletion of Jab1 had no impact on the maturation of normal hematopoietic cells in mice. Mechanistically, Jab1 directly activated IGF2BP3 by driving the transcription factor c-JUN, consequently modulated the m\n                    <jats:sup>6</jats:sup>\n                    A modification of LILRB4 mRNA, and promoted immune evasion in AML. Finally, CSN5i-3 effectively disrupted the signaling pathway mediated by Jab1, thereby restoring cellular immune surveillance and halting the progression of AML. Thus, our results highlight the functional role of Jab1 in supporting AML survival and support the development of targeted therapeutic strategies.\n                  </jats:p>","is_dataset_classified":null,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"40763038","pmcid":"PMC12520683","openalex_id":"https://openalex.org/W4412989569","authors":[],"funders":[{"funder_name":"Innovative Research Group Project of the National Natural Science Foundation of China","grant_id":"82370176","title":null},{"funder_name":"Key Research and Development Program of Hubei Province","grant_id":"2023BCB025","title":null}],"total_grants":2,"fwci":2.3078,"citation_percentile":0.8860035,"influential_citations":0,"citation_trend":[{"year":2025,"count":2},{"year":2026,"count":4}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"http://www.jci.org/articles/view/183761/files/pdf","host_type":"journal"},{"url":"http://www.jci.org/articles/view/183761/files/pdf","host_type":"publisher"},{"url":"https://www.jci.org/articles/view/183761/files/pdf","host_type":"publisher"},{"url":"https://doi.org/10.1172/jci183761","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/40763038","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/12520683","host_type":"repository"},{"url":"https://doaj.org/article/98a1f5a7a8024625aa6f4a1a42b04d48","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC12520683","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC12520683?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["RNA modifications and cancer","Cancer-related molecular mechanisms research","RNA Research and Splicing","COP9 Signalosome Complex","Animals","Leukemia, Myeloid, Acute","Oxidative Stress","Mice","Humans","Intracellular Signaling Peptides and Proteins","Peptide Hydrolases","Mice, Knockout","Disease Progression","Neoplasm Proteins","Immune Evasion","Signal Transduction","Disease Models, Animal","Tumor Escape","Cell Line, Tumor"],"mesh_terms":["COP9 Signalosome Complex","Animals","Disease Models, Animal","Humans","Neoplasm Proteins","Peptide Hydrolases","Signal Transduction","Leukemia, Myeloid, Acute","Mice, Knockout","Oxidative Stress","Disease Progression","Tumor Escape","Cell Line, Tumor","Intracellular Signaling Peptides and Proteins","Mice","Immune Evasion"],"keywords":["Evasion (ethics)","Myeloid leukemia","Oxidative stress","Immune system","Leukemia","Immunology","Myeloid","Myeloid cells","Cancer research","Biology","Medicine","Internal medicine","Cell biology","Signal transduction","Hematology","Cancer gene therapy","Leukemias"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Zero hunger"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"geo"},{"name":"cellosaurus"},{"name":"refseq"},{"name":"nct"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-22T22:19:33.111902Z","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":[]}