{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T09:50:33Z","timestamp":1785750633308,"version":"3.56.0"},"reference-count":23,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T00:00:00Z","timestamp":1780099200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"content-version":"vor","delay-in-days":65,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Huadu District People's Hospital of Guangzhou","award":["YNZDXK202504"],"award-info":[{"award-number":["YNZDXK202504"]}]},{"name":"Huadu District People's Hospital of Guangzhou","award":["YNZDXK202504"],"award-info":[{"award-number":["YNZDXK202504"]}]},{"name":"Huadu District People's Hospital of Guangzhou","award":["YNZDXK202504"],"award-info":[{"award-number":["YNZDXK202504"]}]},{"name":"Huadu District People's Hospital of Guangzhou","award":["YNZDXK202504"],"award-info":[{"award-number":["YNZDXK202504"]}]},{"name":"Huadu District People's Hospital of Guangzhou","award":["YNZDXK202504"],"award-info":[{"award-number":["YNZDXK202504"]}]},{"name":"Huadu District People's Hospital of Guangzhou","award":["YNZDXK202504"],"award-info":[{"award-number":["YNZDXK202504"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Discov Onc"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Acute Myeloid Leukemia (AML) is driven by complex interactions between genetic mutations and epigenetic dysregulation. While alterations in chromatin modifiers are frequent, the precise downstream transcriptional networks they enable and how these networks execute the leukemogenic program remain incompletely defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We employed an integrative bioinformatics strategy. Transcriptomic data from GSE84881 (AML stromal cells) and GSE9476 (AML blasts) identified differentially expressed genes, refined via GeneCards and CellMarker to a 32-gene AML signature. Functional enrichment (GO\/KEGG) and protein-protein interaction (PPI) network analyses followed. Core hubs were validated for spatial (single-cell t-SNE) and subtype-specific expression using the Hematologic Malignancy database. Perturbation analysis (GPSAdb2.0 BioTrigger) expanded the network, with pathway enrichment on responsive genes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The 32-gene signature enriched strongly in hematopoietic differentiation and unexpectedly in cross-lineage developmental pathways (e.g., gland, epithelial development). PPI topology revealed nine hubs: AFF1, TAL1, IKZF1, GATA1, NOTCH1, BCL2, IL1B, IRF4, ZAP70. Single-cell t-SNE showed distinct, non-overlapping localization patterns among AML subpopulations; box plots demonstrated marked expression heterogeneity across 26 molecular subtypes. Perturbation of these hubs generated a 500-gene set whose KEGG enrichment highlighted three interconnected layers: (i) Polycomb repression and ATP-dependent chromatin remodeling (epigenetic gatekeepers), (ii) FoxO signaling, cell cycle, and senescence (core oncogenic pathways), and (iii) broad cancer hallmarks including endocrine resistance and diverse solid tumor pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We propose a hierarchical pathomechanism: synergistic dysfunction in chromatin remodeling and Polycomb-mediated repression establishes a permissive epigenomic landscape, enabling activation of an oncogenic transcriptional network (centered on AFF1, TAL1, IKZF1, GATA1). This network then hijacks TP53\/FoxO signaling to drive cell cycle escape, apoptosis resistance, and metabolic adaptation. Our findings unify disparate molecular lesions into a coherent axis and suggest new therapeutic nodes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s12672-026-05308-2","type":"journal-article","created":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T07:44:46Z","timestamp":1780127086000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["An integrated multi-omics analysis reveals a core epigenetically-activated transcriptional network driving oncogenic signaling in acute myeloid leukemia"],"prefix":"10.1007","volume":"17","author":[{"given":"Lihua","family":"Zeng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haohao","family":"Lei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingnan","family":"Bi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guowei","family":"Run","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bizhen","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linhua","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,30]]},"reference":[{"issue":"24","key":"5308_CR1","doi-asserted-by":"publisher","first-page":"3112","DOI":"10.3390\/diagnostics15243112","volume":"15","author":"S Russo","year":"2025","unstructured":"Russo S, Fazio M, Mirabile G, et al. Bone Marrow Edema and Tyrosine Kinase Inhibitors Treatment in Chronic Myeloid Leukemia. Diagnostics (Basel). 2025;15(24):3112.","journal-title":"Diagnostics (Basel)"},{"issue":"1","key":"5308_CR2","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1182\/hematology.2025000755","volume":"2025","author":"RK Thakur","year":"2025","unstructured":"Thakur RK, Wang ES. The promise of menin inhibitors: from approval to triplet regimens. Hematol Am Soc Hematol Educ Program. 2025;2025(1):599\u2013606.","journal-title":"Hematol Am Soc Hematol Educ Program"},{"issue":"1","key":"5308_CR3","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1007\/s10238-025-01923-5","volume":"26","author":"K Sun","year":"2025","unstructured":"Sun K, Zhou J, Yao H, et al. LncRNA SNHG11 expression in acute myeloid leukemia patients and its relationship with the biology of acute myeloid leukemia cells. 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Biomedicines. 2025;13(12):3007.","journal-title":"Biomedicines"}],"container-title":["Discover Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12672-026-05308-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12672-026-05308-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12672-026-05308-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T09:42:18Z","timestamp":1785750138000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12672-026-05308-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,30]]},"references-count":23,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["5308"],"URL":"https:\/\/doi.org\/10.1007\/s12672-026-05308-2","relation":{},"ISSN":["2730-6011"],"issn-type":[{"value":"2730-6011","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,30]]},"assertion":[{"value":"12 March 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 May 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 May 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This study is based on publicly available datasets from the Gene Expression Omnibus (GSE84881 and GSE9476). The original studies obtained all necessary ethical approvals and informed consent. No new data involving human or animal subjects were collected by the authors; therefore, additional ethical approval was not required for this re-analysis.","order":1,"name":"Ethics","label":"Ethics approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable. This study used only de-identified, publicly available transcriptomic data. The original studies from which the data were derived obtained informed consent from participants.","order":2,"name":"Ethics","label":"Consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable. This manuscript does not contain any individual person\u2019s data in any form (e.g., images, videos, or clinical details).","order":3,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"1103"}}