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Adv."],"published-print":{"date-parts":[[2026,10,23]]},"abstract":"<jats:p>\n                    DNA methylation dynamics shape hematopoietic differentiation and leukemogenesis, yet how the dioxygenase TET2\u2014frequently mutated in myeloid malignancies\u2014directs lineage-specific regulatory programs remains unclear. Here, we integrated DNA methylation, chromatin accessibility, three-dimensional (3D) genome architecture, transcriptional profiling, and TET2 chromatin occupancy to define TET2-dependent control of human myeloid commitment. We found that TET2-bound regulatory regions gain short- and long-range chromatin interactions and that a distinct subset of distal, enhancer-enriched sites undergoes TET2-driven demethylation and activation. Among these, we identified and functionally validated an\n                    <jats:italic toggle=\"yes\">AGO2<\/jats:italic>\n                    myeloid-specific intragenic enhancer that is frequently hypermethylated in patients with\n                    <jats:italic toggle=\"yes\">TET2<\/jats:italic>\n                    -mutant acute myeloid leukemia.\n                    <jats:italic toggle=\"yes\">AGO2<\/jats:italic>\n                    expression stratifies patient survival, and AGO2 depletion abrogates leukemic engraftment in vivo. These findings uncover a TET2-AGO2 regulatory axis that integrates epigenetic remodeling, 3D genome reorganization, and leukemic fitness, and they highlight AGO2 as a potential biomarker and therapeutic target in myeloid leukemia.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aee5701","type":"journal-article","created":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T17:58:42Z","timestamp":1792778322000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["TET2-driven activation of AGO2 links epigenetic remodeling to myeloid commitment and leukemia"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0652-8116","authenticated-orcid":true,"given":"Aleksey","family":"Lazarenkov","sequence":"first","affiliation":[{"name":"Epigenetic Control of Haematopoiesis Group, Josep Carreras Leukaemia Research Institute (IJC), Campus Can Ruti, Badalona, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0494-9128","authenticated-orcid":true,"given":"Gemma","family":"Valc\u00e1rcel","sequence":"additional","affiliation":[{"name":"Epigenetic Control of Haematopoiesis Group, Josep Carreras Leukaemia Research Institute (IJC), Campus Can Ruti, Badalona, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7514-260X","authenticated-orcid":true,"given":"Alba","family":"Martinez","sequence":"additional","affiliation":[{"name":"Stem Cell Biology, Developmental Leukemia and Immunotherapy Group, Josep Carreras Leukaemia Research Institute (IJC), Campus Hospital Cl\u00ednic, Barcelona, Spain."},{"name":"Red de Terapias Avanzadas (TERAV), Instituto de Salud Carlos III, Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4190-8085","authenticated-orcid":true,"given":"Clara","family":"Berenguer","sequence":"additional","affiliation":[{"name":"Epigenetic Control of Haematopoiesis Group, Josep Carreras Leukaemia Research Institute (IJC), Campus Can Ruti, Badalona, Spain."},{"name":"Endocrine Regulatory Genomics, Department of Experimental &amp; 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