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Adv."],"published-print":{"date-parts":[[2026,8,7]]},"abstract":"<jats:p>\n                    The molecular mechanisms by which KMT2A-rearranged (KMT2A-r) leukemias maintain the oncogenic\n                    <jats:italic toggle=\"yes\">FLT3<\/jats:italic>\n                    expression remain largely unclear, limiting therapeutic opportunities. Here, we identify the RNA binding protein MBNL1 as an unexpected positive regulator of\n                    <jats:italic toggle=\"yes\">FLT3<\/jats:italic>\n                    by DepMap dataset exploration and combinatorial CRISPR screens. MBNL1 promotes leukemia cell survival in cell lines and primary tumors by sustaining\n                    <jats:italic toggle=\"yes\">FLT3<\/jats:italic>\n                    expression in a KMT2A-r context-dependent manner. Mechanistically, we discover that MBNL1 recognizes a structured single-stranded DNA (ssDNA) element containing five consecutive guanines within the\n                    <jats:italic toggle=\"yes\">FLT3<\/jats:italic>\n                    enhancer, through MBNL1\u2019s zinc finger domains and the carboxyl-terminal unstructured region. Such MBNL1 protein\/ssDNA interaction was evident in KMT2A-r leukemia using ChIP-seq and KAS-seq. Mutations of key amino acids of MBNL1\u2019s ssDNA binding surface or the critical guanines in ssDNA markedly abrogate the protein-ssDNA interactions. These findings implicate MBNL1 as a distinct\n                    <jats:italic toggle=\"yes\">FLT3<\/jats:italic>\n                    activator by recognizing a structured enhancer ssDNA element, highlighting an unexpected role for RNA binding proteins in transcriptional regulation through direct ssDNA recognition.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aec2331","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T17:59:18Z","timestamp":1786125558000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["MBNL1 hijacks a structured single-stranded distal DNA element to sustain\n                    <i>FLT3<\/i>\n                    expression in KMT2A-rearranged leukemias"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4515-1414","authenticated-orcid":true,"given":"Meixia","family":"Che","sequence":"first","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology, Department of Oncology, Nanjing Drum Tower Hospital, School of Life Sciences, Chemistry and Biomedicine Innovation Center (ChemBIC), Nanjing University, 210023 Nanjing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2213-5515","authenticated-orcid":true,"given":"Shaela","family":"Fields","sequence":"additional","affiliation":[{"name":"Division of Molecular Oncology\/Cancer Biology Program, Comprehensive Cancer Center, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siqi","family":"Yi","sequence":"additional","affiliation":[{"name":"Department of Hematology, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Hyle","sequence":"additional","affiliation":[{"name":"Division of Molecular Oncology\/Cancer Biology Program, Comprehensive Cancer Center, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0801-485X","authenticated-orcid":true,"given":"Mengli","family":"Zhang","sequence":"additional","affiliation":[{"name":"Cyrus Tang Medical Institute, National Clinical, Research Center for Hematologic Disease, State Key Laboratory of Radiation Medicine and Protection, Collaborative Innovation Center of Hematology, Suzhou Medical College, Soochow University, 215123 Suzhou, Jiangsu, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0099-858X","authenticated-orcid":true,"given":"Beisi","family":"Xu","sequence":"additional","affiliation":[{"name":"Center for Applied Bioinformatics, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Hematology, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7573-4813","authenticated-orcid":true,"given":"Peng","family":"Xu","sequence":"additional","affiliation":[{"name":"Cyrus Tang Medical Institute, National Clinical, Research Center for Hematologic Disease, State Key Laboratory of Radiation Medicine and Protection, Collaborative Innovation Center of Hematology, Suzhou Medical College, Soochow University, 215123 Suzhou, Jiangsu, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0886-292X","authenticated-orcid":true,"given":"Yajun","family":"Jiang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology, Department of Oncology, Nanjing Drum Tower Hospital, School of Life Sciences, Chemistry and Biomedicine Innovation Center (ChemBIC), Nanjing University, 210023 Nanjing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5938-5510","authenticated-orcid":true,"given":"Chunliang","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Molecular Oncology\/Cancer Biology Program, Comprehensive Cancer Center, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-011811-132434"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2253"},{"key":"e_1_3_2_4_2","first-page":"121","article-title":"Karyotypic patterns in acute mixed lineage leukemia","volume":"4","author":"Hayashi Y.","year":"1990","unstructured":"Y. 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