{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:59:18Z","timestamp":1791896358400,"version":"4.3.4"},"reference-count":17,"publisher":"American Society of Hematology","issue":"19","license":[{"start":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T00:00:00Z","timestamp":1755129600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,11,6]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>Aberrant activation of BCL11B (BCL11B-a) defines a subtype of lineage-ambiguous leukemias with T-lymphoid and myeloid features, co-occurring activating FLT3 mutations, and a stem\/progenitor immunophenotype and gene expression profile. Similar to other lineage-ambiguous leukemias, optimal treatment is unclear, and there are limited targeted therapeutic options. Here, we investigated the efficacy of B-cell lymphoma 2 (BCL-2) and FMS-like tyrosine kinase 3 (FLT3) inhibition with venetoclax and gilteritinib, respectively, in preclinical models of BCL11B-a leukemia. Despite variation in response to single-agent therapies, the combination of venetoclax plus gilteritinib (VenGilt) was highly effective in all models evaluated. BH3 profiling suggested that resistance to venetoclax monotherapy was due to the tumor-intrinsic dependence on additional BCL-2 family proteins before drug treatment. Longitudinal single-cell RNA sequencing analysis identified mitochondrial pathways and a pro-lymphoid gene expression signature as potential drivers of rare cell survival on VenGilt therapy. These data support clinical evaluation of venetoclax in combination with gilteritinib in BCL11B-a lineage-ambiguous leukemias.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2025028985","type":"journal-article","created":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T21:17:08Z","timestamp":1755206228000},"page":"2350-2356","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":8,"title":["Venetoclax plus gilteritinib is effective in preclinical models of\n                    <i>FLT3<\/i>\n                    -mutant BCL11B-a lineage-ambiguous leukemia"],"prefix":"10.1182","volume":"146","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2342-6349","authenticated-orcid":false,"given":"Lindsey E.","family":"Montefiori","sequence":"first","affiliation":[{"name":"1Department of Pathology, St. Jude Children\u2019s Research Hospital, Memphis, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2008-1365","authenticated-orcid":false,"given":"Ilaria","family":"Iacobucci","sequence":"additional","affiliation":[{"name":"1Department of Pathology, St. Jude Children\u2019s Research Hospital, Memphis, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9930-8499","authenticated-orcid":false,"given":"Qingsong","family":"Gao","sequence":"additional","affiliation":[{"name":"1Department of Pathology, St. Jude Children\u2019s Research Hospital, Memphis, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamila","family":"Moore","sequence":"additional","affiliation":[{"name":"2Preclinical Therapeutics Program, St. Jude Children\u2019s Research Hospital, Memphis, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2274-9966","authenticated-orcid":false,"given":"William C.","family":"Wright","sequence":"additional","affiliation":[{"name":"3Department of Computational Biology, St. Jude Children\u2019s Research Hospital, Memphis, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huimei","family":"Wei","sequence":"additional","affiliation":[{"name":"1Department of Pathology, St. Jude Children\u2019s Research Hospital, Memphis, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pradyumna","family":"Baviskar","sequence":"additional","affiliation":[{"name":"1Department of Pathology, St. Jude Children\u2019s Research Hospital, Memphis, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6644-8970","authenticated-orcid":false,"given":"Surbhi","family":"Sona","sequence":"additional","affiliation":[{"name":"4Center for Applied Bioinformatics, St. Jude Children\u2019s Research Hospital, Memphis, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3833-7170","authenticated-orcid":false,"given":"Hongjian","family":"Jin","sequence":"additional","affiliation":[{"name":"4Center for Applied Bioinformatics, St. Jude Children\u2019s Research Hospital, Memphis, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit","family":"Budhraja","sequence":"additional","affiliation":[{"name":"5Department of Cell and Molecular Biology, St. Jude Children\u2019s Research Hospital, Memphis, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2504-8657","authenticated-orcid":false,"given":"Josi","family":"Lott","sequence":"additional","affiliation":[{"name":"6Center of Excellence for Leukemia Studies, St. Jude Children\u2019s Research Hospital, Memphis, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi Zhang","family":"Tatarata","sequence":"additional","affiliation":[{"name":"7Department of Medicine, State University of New York Downstate Health Sciences University, Brooklyn, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongshan","family":"Cheng","sequence":"additional","affiliation":[{"name":"4Center for Applied Bioinformatics, St. Jude Children\u2019s Research Hospital, Memphis, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanya","family":"Khan","sequence":"additional","affiliation":[{"name":"1Department of Pathology, St. Jude Children\u2019s Research Hospital, Memphis, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1253-9148","authenticated-orcid":false,"given":"Emily A.","family":"Backhaus Wagner","sequence":"additional","affiliation":[{"name":"1Department of Pathology, St. Jude Children\u2019s Research Hospital, Memphis, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Johnson","sequence":"additional","affiliation":[{"name":"8Center for In Vivo Imaging and Therapeutics, St. Jude Children\u2019s Research Hospital, Memphis, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyrus M.","family":"Mehr","sequence":"additional","affiliation":[{"name":"1Department of Pathology, St. Jude Children\u2019s Research Hospital, Memphis, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2174-5119","authenticated-orcid":false,"given":"Burgess","family":"Freeman","sequence":"additional","affiliation":[{"name":"9Preclinical Pharmacokinetic Shared Resource, St. Jude Children\u2019s Research Hospital, Memphis, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Janke","sequence":"additional","affiliation":[{"name":"10Comparative Pathology Core, St. Jude Children\u2019s Research Hospital, Memphis, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torsten","family":"Haferlach","sequence":"additional","affiliation":[{"name":"11Munich Leukemia Laboratory, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Geeleher","sequence":"additional","affiliation":[{"name":"3Department of Computational Biology, St. Jude Children\u2019s Research Hospital, Memphis, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul E.","family":"Mead","sequence":"additional","affiliation":[{"name":"1Department of Pathology, St. Jude Children\u2019s Research Hospital, Memphis, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9347-2212","authenticated-orcid":false,"given":"Marina","family":"Konopleva","sequence":"additional","affiliation":[{"name":"12Department of Oncology, Albert Einstein College of Medicine, Bronx, NY"},{"name":"13Department of Molecular Pharmacology, 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