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Adv."],"published-print":{"date-parts":[[2026,5,8]]},"abstract":"<jats:p>\n                    Oncogenic fusion transcription factors (TFs) frequently drive hematopoietic malignancies by altering gene expression in key developmental programs. TCF3::HLF is a fusion TF that characterizes a rare, treatment-resistant subtype of B cell acute lymphoblastic leukemia [t(17;19) TCF3::HLF-positive B-ALL]. Despite its clinical significance, the mechanisms by which TCF3::HLF induces leukemia are unclear. We used HiChIP mapping and genetic interference to analyze TCF3::HLF at the 3D genome level, revealing enhancer-promoter interactions that control gene activation or repression. Notably, TCF3::HLF directly regulates\n                    <jats:italic toggle=\"yes\">MEF2C<\/jats:italic>\n                    expression through its enhancer, as interference disrupted\n                    <jats:italic toggle=\"yes\">MEF2C<\/jats:italic>\n                    transcription and inhibited leukemia propagation. This disruption also diminished embryonal hematopoietic stem cell (HSC) gene signatures and restored mature HSC and B-lymphoid markers. These findings highlight\n                    <jats:italic toggle=\"yes\">MEF2C<\/jats:italic>\n                    as a critical component of the transcriptional network reprogrammed by TCF3::HLF. Our study provides insight into how TCF3::HLF rewires the 3D genome to drive leukemia and serves as a resource for further exploration of the TCF3::HLF regulome.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.adu3728","type":"journal-article","created":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T17:59:26Z","timestamp":1778090366000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":2,"title":["TCF3::HLF orchestrates an enhancer-promoter network with activation of MEF2C to promote immature HSC gene expression in leukemia"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8763-0026","authenticated-orcid":true,"given":"Valdemar","family":"Priebe","sequence":"first","affiliation":[{"name":"Division of Oncology and Children\u2019s Research Centre, University Children\u2019s Hospital Zurich, Zurich, Switzerland."},{"name":"Department of Molecular Mechanism of Disease, University of Zurich, Zurich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8629-4860","authenticated-orcid":true,"given":"Bartim\u00e9e","family":"Galvan","sequence":"additional","affiliation":[{"name":"Division of Oncology and Children\u2019s Research Centre, University Children\u2019s Hospital Zurich, Zurich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4783-1492","authenticated-orcid":true,"given":"Aneta","family":"Drakul","sequence":"additional","affiliation":[{"name":"Division of Oncology and Children\u2019s Research Centre, University Children\u2019s Hospital Zurich, Zurich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2123-0351","authenticated-orcid":true,"given":"Nicola","family":"Margelisch","sequence":"additional","affiliation":[{"name":"Division of Oncology and Children\u2019s Research Centre, University Children\u2019s Hospital Zurich, Zurich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5600-4279","authenticated-orcid":true,"given":"J\u00falia","family":"Aguad\u00e9-Gorgori\u00f3","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA."},{"name":"Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5097-524X","authenticated-orcid":true,"given":"Kaivalya","family":"Walavalkar","sequence":"additional","affiliation":[{"name":"Department of Molecular Mechanism of Disease, University of Zurich, Zurich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5987-1319","authenticated-orcid":true,"given":"Yun","family":"Huang","sequence":"additional","affiliation":[{"name":"Division of Oncology and Children\u2019s Research Centre, University Children\u2019s Hospital Zurich, Zurich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3400-1496","authenticated-orcid":true,"given":"Hanna K. A.","family":"Mikkola","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA."},{"name":"Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA, USA."},{"name":"Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, USA."},{"name":"Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2890-3191","authenticated-orcid":true,"given":"Beat","family":"Bornhauser","sequence":"additional","affiliation":[{"name":"Division of Oncology and Children\u2019s Research Centre, University Children\u2019s Hospital Zurich, Zurich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9894-2896","authenticated-orcid":true,"given":"Raffaella","family":"Santoro","sequence":"additional","affiliation":[{"name":"Department of Molecular Mechanism of Disease, University of Zurich, Zurich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6571-6227","authenticated-orcid":true,"given":"Jean-Pierre","family":"Bourquin","sequence":"additional","affiliation":[{"name":"Division of Oncology and Children\u2019s Research Centre, University Children\u2019s Hospital Zurich, Zurich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1182-7"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2021.03.005"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3963"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-020-0602-9"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-24044-5"},{"key":"e_1_3_2_7_2","first-page":"47","article-title":"Recent advances in the biology and treatment of B-cell acute lymphoblastic leukemia","volume":"8","author":"Hefazi M.","year":"2018","unstructured":"M. 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