{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:43:32Z","timestamp":1785437012969,"version":"3.56.0"},"reference-count":80,"publisher":"Rockefeller University Press","issue":"4","license":[{"start":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T00:00:00Z","timestamp":1739923200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/rupress.org\/pages\/terms102024"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01CA196604"],"award-info":[{"award-number":["R01CA196604"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01CA27611701"],"award-info":[{"award-number":["R01CA27611701"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["RO1CA228135"],"award-info":[{"award-number":["RO1CA228135"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["PO1CA229086"],"award-info":[{"award-number":["PO1CA229086"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["RO1CA242020"],"award-info":[{"award-number":["RO1CA242020"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["RO1CA252239"],"award-info":[{"award-number":["RO1CA252239"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI136941"],"award-info":[{"award-number":["R01AI136941"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Michigan Medicine Rogel Cancer Center"},{"DOI":"10.13039\/100001445","name":"Alex\u2019s Lemonade Stand","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001445","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100003287","name":"Rally Foundation for Childhood Cancer Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100003287","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["26533"],"award-info":[{"award-number":["26533"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32GM145470"],"award-info":[{"award-number":["T32GM145470"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["F31CA260929"],"award-info":[{"award-number":["F31CA260929"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["F30-CA-268782"],"award-info":[{"award-number":["F30-CA-268782"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["X01HD100702"],"award-info":[{"award-number":["X01HD100702"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005410","name":"American-Italian Cancer Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005410","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Vogelstein Family Foundation"},{"DOI":"10.13039\/100006058","name":"St. Baldricks Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006058","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001445","name":"Alex\u2019s Lemonade Stand Foundation for childhood cancer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001445","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,4,7]]},"abstract":"<jats:p>While the mutational landscape across early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) and ETP-like leukemia is known, establishing a unified framework that activates stem cell genes characteristic of these tumors remains elusive. Using complementary mouse and human models, chromatin mapping, and enhancer profiling, we show that the coactivator ZMIZ1 promotes normal and malignant ETP population growth by inducing the transcription factor MYB in feedforward circuits to convergently activate oncogenes (MEF2C, MYCN, and BCL2) through essential enhancers. A key superenhancer, the N-Myc regulating enhancer (NMRE), drives malignant ETP population growth but is dispensable for normal lymphopoiesis. This network of stem cell superenhancers identifies treatment-resistant tumors and poor survival outcomes; unifies diverse ETP-ALLs; and contributes to cardinal features of the recently genomically identified high-risk bone marrow progenitor-like (BMP-like) ETP-ALL tumor\u2014stem cell\/myeloid gene expression, inhibited NOTCH1-induced T-cell development, aggressive clinical behavior, and venetoclax sensitivity. Since ZMIZ1 is dispensable for essential homeostasis, it might be possible to safely target this network to treat high-risk diseases.<\/jats:p>","DOI":"10.1084\/jem.20231349","type":"journal-article","created":{"date-parts":[[2025,1,3]],"date-time":"2025-01-03T02:20:43Z","timestamp":1735870843000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":6,"title":["Native stem cell transcriptional circuits define cardinal features of high-risk leukemia"],"prefix":"10.1084","volume":"222","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5520-4495","authenticated-orcid":true,"given":"Qing","family":"Wang","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/028p1nc07","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Michigan School of Medicine 1 Division of Hematology-Oncology, Department of Internal Medicine, , Ann Arbor, MI,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1732-2033","authenticated-orcid":true,"given":"Francesco","family":"Boccalatte","sequence":"additional","affiliation":[{"name":"NYU Grossman School of Medicine 2 Department of Pathology, , New York, NY,","place":["USA"]},{"name":"Candiolo Cancer Institute, FPO-IRCCS 3 , Turin,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9061-3593","authenticated-orcid":true,"given":"Jason","family":"Xu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00b30xv10","id-type":"ROR","asserted-by":"publisher"}],"name":"Graduate Group in Genomics and Computational Biology, Perelman School of Medicine, University of Pennsylvania 4 , Philadelphia, PA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2318-0003","authenticated-orcid":true,"given":"Giovanni","family":"Gambi","sequence":"additional","affiliation":[{"name":"NYU Grossman School of Medicine 2 Department of Pathology, , New York, NY,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1974-8425","authenticated-orcid":true,"given":"Bettina","family":"Nadorp","sequence":"additional","affiliation":[{"name":"NYU Grossman School of Medicine 2 Department of Pathology, , New York, NY,","place":["USA"]},{"name":"New York University Grossman School of Medicine 5 Division of Precision Medicine, Department of Medicine, , New York, NY,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6080-8164","authenticated-orcid":true,"given":"Fatema","family":"Akter","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/028p1nc07","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Michigan School of Medicine 1 Division of Hematology-Oncology, Department of Internal Medicine, , Ann Arbor, MI,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4487-2779","authenticated-orcid":true,"given":"Carea","family":"Mullin","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/028p1nc07","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Michigan School of Medicine 1 Division of Hematology-Oncology, Department of Internal Medicine, , Ann Arbor, MI,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5880-3074","authenticated-orcid":true,"given":"Ashley F.","family":"Melnick","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/028p1nc07","id-type":"ROR","asserted-by":"publisher"}],"name":"Cellular and Molecular Biology Program, University of Michigan School of Medicine 6 , Ann Arbor, MI,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0808-0740","authenticated-orcid":true,"given":"Elizabeth","family":"Choe","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00jmfr291","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Michigan 7 Department of Computational Medicine and Bioinformatics, , Ann Arbor, MI,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3828-9797","authenticated-orcid":true,"given":"Anna C.","family":"McCarter","sequence":"additional","affiliation":[{"name":"Stanford University 8 Department of Anesthesiology, Perioperative and Pain Medicine, , Stanford, CA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9251-0408","authenticated-orcid":true,"given":"Nicole A.","family":"Jerome","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/028p1nc07","id-type":"ROR","asserted-by":"publisher"}],"name":"Cancer Biology Program, University of Michigan School of Medicine 9 , Ann Arbor, MI,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0153-6152","authenticated-orcid":true,"given":"Siyi","family":"Chen","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/028p1nc07","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Michigan School of Medicine 1 Division of Hematology-Oncology, Department of Internal Medicine, , Ann Arbor, MI,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8429-6325","authenticated-orcid":true,"given":"Karena","family":"Lin","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/028p1nc07","id-type":"ROR","asserted-by":"publisher"}],"name":"Cellular and Molecular Biology Program, University of Michigan School of Medicine 6 , Ann Arbor, MI,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6018-7290","authenticated-orcid":true,"given":"Sarah","family":"Khan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/028p1nc07","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Michigan School of Medicine 1 Division of Hematology-Oncology, Department of Internal Medicine, , Ann Arbor, MI,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1711-8641","authenticated-orcid":true,"given":"Rohan","family":"Kodgule","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00jmfr291","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Michigan 10 Department of Pathology, , Ann Arbor, MI,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3057-3550","authenticated-orcid":true,"given":"Jonathan H.","family":"Sussman","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00b30xv10","id-type":"ROR","asserted-by":"publisher"}],"name":"Graduate Group in Genomics and Computational Biology, Perelman School of Medicine, University of Pennsylvania 4 , Philadelphia, PA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6128-9985","authenticated-orcid":true,"given":"Petri","family":"P\u00f6l\u00f6nen","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02r3e0967","id-type":"ROR","asserted-by":"publisher"}],"name":"St Jude Children\u2019s Research Hospital 11 Department of Pathology, , Memphis, TN,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5549-0463","authenticated-orcid":true,"given":"Javier","family":"Rodriguez-Hernaez","sequence":"additional","affiliation":[{"name":"NYU Grossman School of Medicine 2 Department of Pathology, , New York, NY,","place":["USA"]},{"name":"New York University Grossman School of Medicine 5 Division of Precision Medicine, Department of Medicine, , New York, NY,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1138-0067","authenticated-orcid":true,"given":"Sonali","family":"Narang","sequence":"additional","affiliation":[{"name":"NYU Grossman School of Medicine 2 Department of Pathology, , New York, NY,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4422-5064","authenticated-orcid":true,"given":"Kleopatra","family":"Avrampou","sequence":"additional","affiliation":[{"name":"NYU Grossman School of Medicine 2 Department of Pathology, , New York, NY,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1203-784X","authenticated-orcid":true,"given":"Bryan","family":"King","sequence":"additional","affiliation":[{"name":"NYU Grossman School of Medicine 2 Department of Pathology, , New York, NY,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7512-8477","authenticated-orcid":true,"given":"Aristotelis","family":"Tsirigos","sequence":"additional","affiliation":[{"name":"NYU Grossman School of Medicine 2 Department of Pathology, , New York, NY,","place":["USA"]},{"name":"New York University Grossman School of Medicine 5 Division of Precision Medicine, Department of Medicine, , New York, NY,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8174-3962","authenticated-orcid":true,"given":"Russell J.H.","family":"Ryan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00jmfr291","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Michigan 10 Department of Pathology, , Ann Arbor, MI,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1871-1850","authenticated-orcid":true,"given":"Charles G.","family":"Mullighan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02r3e0967","id-type":"ROR","asserted-by":"publisher"}],"name":"St Jude Children\u2019s Research Hospital 11 Department of Pathology, , Memphis, TN,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7373-8987","authenticated-orcid":true,"given":"David T.","family":"Teachey","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01z7r7q48","id-type":"ROR","asserted-by":"publisher"}],"name":"Children\u2019s Hospital of Philadelphia 12 Department of Pediatrics, , Philadelphia, PA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9104-5567","authenticated-orcid":true,"given":"Kai","family":"Tan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01z7r7q48","id-type":"ROR","asserted-by":"publisher"}],"name":"Children\u2019s Hospital of Philadelphia 12 Department of Pediatrics, , Philadelphia, PA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6857-1035","authenticated-orcid":true,"given":"Iannis","family":"Aifantis","sequence":"additional","affiliation":[{"name":"NYU Grossman School of Medicine 2 Department of Pathology, , New York, NY,","place":["USA"]},{"id":[{"id":"https:\/\/ror.org\/005dvqh91","id-type":"ROR","asserted-by":"publisher"}],"name":"Perlmutter Cancer Center, NYU Langone Health 13 , New York, NY,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2099-0956","authenticated-orcid":true,"given":"Mark Y.","family":"Chiang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/028p1nc07","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Michigan School of Medicine 1 Division of Hematology-Oncology, Department of Internal Medicine, , Ann Arbor, MI,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2025,2,19]]},"reference":[{"key":"2025021914460983200_bib1","doi-asserted-by":"publisher","first-page":"2896","DOI":"10.4049\/jimmunol.171.6.2896","article-title":"Notch signaling augments T cell responsiveness by enhancing CD25 expression","volume":"171","author":"Adler","year":"2003","journal-title":"J. Immunol."},{"key":"2025021914460983200_bib2","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.1038\/nmeth.4463","article-title":"SCENIC: Single-cell regulatory network inference and clustering","volume":"14","author":"Aibar","year":"2017","journal-title":"Nat. Methods"},{"key":"2025021914460983200_bib79","doi-asserted-by":"publisher","first-page":"9354","DOI":"10.1038\/s41598-019-45839-z","article-title":"The ENCODE blacklist: Identification of problematic regions of the genome","volume":"9","author":"Amemiya","year":"2019","journal-title":"Sci. Rep."},{"key":"2025021914460983200_bib3","doi-asserted-by":"publisher","first-page":"2463","DOI":"10.1182\/blood.2019004547","article-title":"Single-cell RNA-seq reveals developmental plasticity with coexisting oncogenic states and immune evasion programs in ETP-ALL","volume":"137","author":"Anand","year":"2021","journal-title":"Blood"},{"key":"2025021914460983200_bib4","doi-asserted-by":"publisher","first-page":"1145","DOI":"10.1038\/leu.2013.377","article-title":"BCL2-specific inhibitor ABT-199 synergizes strongly with cytarabine against the early immature LOUCY cell line but not more-differentiated T-ALL cell lines","volume":"28","author":"Anderson","year":"2014","journal-title":"Leukemia"},{"key":"2025021914460983200_bib5","doi-asserted-by":"publisher","first-page":"1118","DOI":"10.3390\/genes12081118","article-title":"T-cell acute lymphoblastic leukemia: Biomarkers and their clinical usefulness","volume":"12","author":"Bardelli","year":"2021","journal-title":"Genes"},{"key":"2025021914460983200_bib6","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1016\/j.chembiol.2020.09.001","article-title":"Discovery of a functional covalent ligand targeting an intrinsically disordered cysteine within MYC","volume":"28","author":"Boike","year":"2020","journal-title":"Cell Chem Biol."},{"key":"2025021914460983200_bib7","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.150363","article-title":"MEF2C opposes Notch in lymphoid lineage decision and drives leukemia in the thymus","volume":"7","author":"Cante-Barrett","year":"2022","journal-title":"JCI Insight"},{"key":"2025021914460983200_bib8","doi-asserted-by":"publisher","first-page":"1479","DOI":"10.1016\/j.cell.2013.12.001","article-title":"Dynamic imaging of genomic loci in living human cells by an optimized CRISPR\/Cas system","volume":"155","author":"Chen","year":"2013","journal-title":"Cell"},{"key":"2025021914460983200_bib9","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1182\/blood-2012-03-416503","article-title":"Divergent effects of supraphysiologic Notch signals on leukemia stem cells and hematopoietic stem cells","volume":"121","author":"Chiang","year":"2013","journal-title":"Blood"},{"key":"2025021914460983200_bib10","doi-asserted-by":"publisher","first-page":"1074","DOI":"10.1158\/2159-8290.CD-14-0353","article-title":"Maturation stage of T-cell acute lymphoblastic leukemia determines BCL-2 versus BCL-XL dependence and sensitivity to ABT-199","volume":"4","author":"Chonghaile","year":"2014","journal-title":"Cancer Discov."},{"key":"2025021914460983200_bib11","doi-asserted-by":"publisher","first-page":"1541","DOI":"10.1038\/s41375-022-01554-9","article-title":"Identification of a c-MYB-directed therapeutic for acute myeloid leukemia","volume":"36","author":"Clesham","year":"2022","journal-title":"Leukemia"},{"key":"2025021914460983200_bib12","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/S1470-2045(08)70314-0","article-title":"Early T-cell precursor leukaemia: A subtype of very high-risk acute lymphoblastic leukaemia","volume":"10","author":"Coustan-Smith","year":"2009","journal-title":"Lancet Oncol."},{"key":"2025021914460983200_bib13","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1002\/immu.200310005","article-title":"Transgenic mice with hematopoietic and lymphoid specific expression of Cre","volume":"33","author":"de Boer","year":"2003","journal-title":"Eur. J. Immunol."},{"key":"2025021914460983200_bib80","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.molcel.2024.11.040","article-title":"3D chromatin hubs as regulatory units of identity and survival in human acute leukemia","volume":"85","author":"Gambi","year":"2025","journal-title":"Mol. Cell"},{"key":"2025021914460983200_bib14","doi-asserted-by":"publisher","first-page":"3573","DOI":"10.1016\/j.cell.2021.04.048","article-title":"Integrated analysis of multimodal single-cell data","volume":"184","author":"Hao","year":"2021","journal-title":"Cell"},{"key":"2025021914460983200_bib15","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1097\/MOH.0b013e3283623c61","article-title":"Early T-cell precursor acute lymphoblastic leukaemia","volume":"20","author":"Haydu","year":"2013","journal-title":"Curr. Opin. Hematol."},{"key":"2025021914460983200_bib16","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.yexcr.2018.05.006","article-title":"Mebendazole exhibits potent anti-leukemia activity on acute myeloid leukemia","volume":"369","author":"He","year":"2018","journal-title":"Exp. Cell Res."},{"key":"2025021914460983200_bib17","doi-asserted-by":"publisher","first-page":"1130","DOI":"10.1038\/nm.3665","article-title":"A NOTCH1-driven MYC enhancer promotes T cell development, transformation and acute lymphoblastic leukemia","volume":"20","author":"Herranz","year":"2014","journal-title":"Nat. Med."},{"key":"2025021914460983200_bib18","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1016\/j.ccr.2011.02.008","article-title":"Integrated transcript and genome analyses reveal NKX2-1 and MEF2C as potential oncogenes in T cell acute lymphoblastic leukemia","volume":"19","author":"Homminga","year":"2011","journal-title":"Cancer Cell"},{"key":"2025021914460983200_bib19","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1038\/s41577-020-00426-6","article-title":"How transcription factors drive choice of the T cell fate","volume":"21","author":"Hosokawa","year":"2021","journal-title":"Nat. Rev. Immunol."},{"key":"2025021914460983200_bib20","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1016\/j.immuni.2018.01.013","article-title":"Transformation of accessible chromatin and 3D nucleome underlies lineage commitment of early T cells","volume":"48","author":"Hu","year":"2018","journal-title":"Immunity"},{"key":"2025021914460983200_bib21","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1016\/j.immuni.2018.01.012","article-title":"Lineage-determining transcription factor TCF-1 initiates the epigenetic identity of T cells","volume":"48","author":"Johnson","year":"2018","journal-title":"Immunity"},{"key":"2025021914460983200_bib22","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/S0145-2126(98)00146-5","article-title":"Alterations of the p53, p21, p16, p15 and RAS genes in childhood T-cell acute lymphoblastic leukemia","volume":"23","author":"Kawamura","year":"1999","journal-title":"Leuk. Res."},{"key":"2025021914460983200_bib23","doi-asserted-by":"publisher","first-page":"1312","DOI":"10.1038\/ni.3559","article-title":"The ubiquitin ligase Huwe1 regulates the maintenance and lymphoid commitment of hematopoietic stem cells","volume":"17","author":"King","year":"2016","journal-title":"Nat. Immunol."},{"key":"2025021914460983200_bib24","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1038\/nature09999","article-title":"A novel tumour-suppressor function for the Notch pathway in myeloid leukaemia","volume":"473","author":"Klinakis","year":"2011","journal-title":"Nature"},{"key":"2025021914460983200_bib25","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1038\/s41588-020-0602-9","article-title":"Three-dimensional chromatin landscapes in T cell acute lymphoblastic leukemia","volume":"52","author":"Kloetgen","year":"2020","journal-title":"Nat. Genet."},{"key":"2025021914460983200_bib26","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1158\/2643-3230.BCD-21-0224","article-title":"ETV6 deficiency unlocks ERG-dependent microsatellite enhancers to drive aberrant gene activation in B-lymphoblastic leukemia","volume":"4","author":"Kodgule","year":"2023","journal-title":"Blood Cancer Discov."},{"key":"2025021914460983200_bib78","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1038\/nmeth.1923","article-title":"Fast gapped-read alignment with Bowtie 2","volume":"9","author":"Langmead","year":"2012","journal-title":"Nat. Methods"},{"key":"2025021914460983200_bib27","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1038\/s43018-023-00518-x","article-title":"An inflammatory state remodels the immune microenvironment and improves risk stratification in acute myeloid leukemia","volume":"4","author":"Lasry","year":"2023","journal-title":"Nat. Cancer"},{"key":"2025021914460983200_bib28","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1016\/j.stem.2008.09.005","article-title":"Hematopoietic stem cell function and survival depend on c-Myc and N-Myc activity","volume":"3","author":"Laurenti","year":"2008","journal-title":"Cell Stem Cell"},{"key":"2025021914460983200_bib29","doi-asserted-by":"publisher","first-page":"1088","DOI":"10.1016\/j.immuni.2020.03.019","article-title":"Integrated scRNA-seq identifies human postnatal thymus seeding progenitors and regulatory dynamics of differentiating immature thymocytes","volume":"52","author":"Lavaert","year":"2020","journal-title":"Immunity"},{"key":"2025021914460983200_bib30","doi-asserted-by":"publisher","first-page":"4523","DOI":"10.1093\/nar\/gkm476","article-title":"The novel PIAS-like protein hZimp10 is a transcriptional co-activator of the p53 tumor suppressor","volume":"35","author":"Lee","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"2025021914460983200_bib31","doi-asserted-by":"publisher","first-page":"918","DOI":"10.1182\/blood-2012-03-418103","article-title":"LRF-mediated Dll4 repression in erythroblasts is necessary for hematopoietic stem cell maintenance","volume":"121","author":"Lee","year":"2013","journal-title":"Blood"},{"key":"2025021914460983200_bib32","doi-asserted-by":"publisher","first-page":"998","DOI":"10.1158\/2159-8290.CD-19-0789","article-title":"EZH2 deficient T-cell acute lymphoblastic leukemia is sensitized to CHK1 inhibition through enhanced replication stress","volume":"10","author":"Le\u00f3n","year":"2020","journal-title":"Cancer Discov."},{"key":"2025021914460983200_bib33","doi-asserted-by":"publisher","first-page":"23748","DOI":"10.1074\/jbc.M508365200","article-title":"The novel PIAS-like protein hZimp10 enhances Smad transcriptional activity","volume":"281","author":"Li","year":"2006","journal-title":"J. Biol. Chem."},{"key":"2025021914460983200_bib34","doi-asserted-by":"publisher","first-page":"21689","DOI":"10.1073\/pnas.0907623106","article-title":"Conditional c-myb knockout in adult hematopoietic stem cells leads to loss of self-renewal due to impaired proliferation and accelerated differentiation","volume":"106","author":"Lieu","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025021914460983200_bib35","doi-asserted-by":"publisher","first-page":"1211","DOI":"10.1038\/ng.3909","article-title":"The genomic landscape of pediatric and young adult T-lineage acute lymphoblastic leukemia","volume":"49","author":"Liu","year":"2017","journal-title":"Nat. Genet."},{"key":"2025021914460983200_bib36","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1007\/s00109-022-02216-0","article-title":"ZMIZ proteins: Partners in transcriptional regulation and risk factors for human disease","volume":"100","author":"Lomel\u00ed","year":"2022","journal-title":"J. Mol. Med."},{"key":"2025021914460983200_bib37","doi-asserted-by":"publisher","first-page":"2239","DOI":"10.1084\/jem.20061020","article-title":"The requirement for Notch signaling at the beta-selection checkpoint in vivo is absolute and independent of the pre-T cell receptor","volume":"203","author":"Maillard","year":"2006","journal-title":"J. Exp. Med."},{"key":"2025021914460983200_bib38","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1007\/978-1-4939-2809-5_17","article-title":"Intrathymic injection","volume":"1323","author":"Manna","year":"2016","journal-title":"Methods Mol. Biol."},{"key":"2025021914460983200_bib39","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1158\/2643-3230.BCD-20-0026","article-title":"Combinatorial ETS1-dependent control of oncogenic NOTCH1 enhancers in T-cell leukemia","volume":"1","author":"McCarter","year":"2020","journal-title":"Blood Cancer Discov."},{"key":"2025021914460983200_bib40","doi-asserted-by":"publisher","first-page":"2093","DOI":"10.1182\/blood-2012-09-458570","article-title":"Requirement for Lyl1 in a model of Lmo2-driven early T-cell precursor ALL","volume":"122","author":"McCormack","year":"2013","journal-title":"Blood"},{"key":"2025021914460983200_bib41","doi-asserted-by":"publisher","first-page":"879","DOI":"10.1126\/science.1182378","article-title":"The Lmo2 oncogene initiates leukemia in mice by inducing thymocyte self-renewal","volume":"327","author":"McCormack","year":"2010","journal-title":"Science"},{"key":"2025021914460983200_bib42","doi-asserted-by":"publisher","first-page":"867","DOI":"10.4049\/jimmunol.1000782","article-title":"Direct comparison of Dll1- and Dll4-mediated Notch activation levels shows differential lymphomyeloid lineage commitment outcomes","volume":"185","author":"Mohtashami","year":"2010","journal-title":"J. Immunol."},{"key":"2025021914460983200_bib43","doi-asserted-by":"publisher","first-page":"2846","DOI":"10.1158\/2159-8290.CD-21-0145","article-title":"Enhancer hijacking drives oncogenic BCL11B expression in lineage-ambiguous stem cell leukemia","volume":"11","author":"Montefiori","year":"2021","journal-title":"Cancer Discov."},{"key":"2025021914460983200_bib44","doi-asserted-by":"publisher","first-page":"14943","DOI":"10.1073\/pnas.96.26.14943","article-title":"Constitutive Bcl-2 expression throughout the hematopoietic compartment affects multiple lineages and enhances progenitor cell survival","volume":"96","author":"Ogilvy","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025021914460983200_bib45","doi-asserted-by":"publisher","first-page":"3224","DOI":"10.1126\/science.aay3224","article-title":"A cell atlas of human thymic development defines T cell repertoire formation","volume":"367","author":"Park","year":"2020","journal-title":"Science"},{"key":"2025021914460983200_bib46","doi-asserted-by":"publisher","first-page":"870","DOI":"10.1016\/j.immuni.2015.10.007","article-title":"The PIAS-like coactivator Zmiz1 is a direct and selective cofactor of Notch1 in T cell development and leukemia","volume":"43","author":"Pinnell","year":"2015","journal-title":"Immunity"},{"key":"2025021914460983200_bib47","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1111\/bjh.17310","article-title":"Current and emerging therapeutic approaches for T-cell acute lymphoblastic leukaemia","volume":"194","author":"Pocock","year":"2021","journal-title":"Br. J. Haematol."},{"key":"2025021914460983200_bib48","doi-asserted-by":"publisher","first-page":"1082","DOI":"10.1038\/s41586-024-07807-0","article-title":"The genomic basis of childhood T-lineage acute lymphoblastic leukaemia","volume":"632","author":"P\u00f6l\u00f6nen","year":"2024","journal-title":"Nature"},{"key":"2025021914460983200_bib49","doi-asserted-by":"publisher","first-page":"930","DOI":"10.1158\/0008-5472.CAN-12-1389","article-title":"Convergence of the ZMIZ1 and NOTCH1 pathways at C-MYC in acute T lymphoblastic leukemias","volume":"73","author":"Rakowski","year":"2013","journal-title":"Cancer Res."},{"key":"2025021914460983200_bib50","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1038\/s41467-017-02618-6","article-title":"Peptidomimetic blockade of MYB in acute myeloid leukemia","volume":"9","author":"Ramaswamy","year":"2018","journal-title":"Nat. Commun."},{"key":"2025021914460983200_bib51","doi-asserted-by":"publisher","first-page":"856","DOI":"10.1158\/2159-8290.CD-21-0551","article-title":"Intracellular cholesterol pools regulate oncogenic signaling and epigenetic circuitries in Early T-cell Precursor Acute Lymphoblastic Leukemia","volume":"12","author":"Rashkovan","year":"2022","journal-title":"Cancer Discov."},{"key":"2025021914460983200_bib52","doi-asserted-by":"publisher","first-page":"1280","DOI":"10.1038\/s41590-020-0747-9","article-title":"Distinct and temporary-restricted epigenetic mechanisms regulate human \u03b1\u03b2 and \u03b3\u03b4 T cell development","volume":"21","author":"Roels","year":"2020","journal-title":"Nat. Immunol."},{"key":"2025021914460983200_bib53","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1016\/bs.ai.2015.09.002","article-title":"Forging T-Lymphocyte identity: Intersecting networks of transcriptional control","volume":"129","author":"Rothenberg","year":"2016","journal-title":"Adv. Immunol."},{"key":"2025021914460983200_bib54","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1016\/j.ccr.2012.06.007","article-title":"Core transcriptional regulatory circuit controlled by the TAL1 complex in human T cell acute lymphoblastic leukemia","volume":"22","author":"Sanda","year":"2012","journal-title":"Cancer Cell"},{"key":"2025021914460983200_bib55","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1016\/j.immuni.2010.03.005","article-title":"Fate mapping reveals separate origins of T cells and myeloid lineages in the thymus","volume":"32","author":"Schlenner","year":"2010","journal-title":"Immunity"},{"key":"2025021914460983200_bib56","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1016\/S1074-7613(02)00474-0","article-title":"Induction of T cell development from hematopoietic progenitor cells by delta-like-1 in vitro","volume":"17","author":"Schmitt","year":"2002","journal-title":"Immunity"},{"key":"2025021914460983200_bib57","doi-asserted-by":"publisher","first-page":"6101","DOI":"10.1093\/emboj\/cdg585","article-title":"hZimp10 is an androgen receptor co-activator and forms a complex with SUMO-1 at replication foci","volume":"22","author":"Sharma","year":"2003","journal-title":"EMBO J."},{"key":"2025021914460983200_bib58","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0085883","article-title":"LIM domain only-2 (LMO2) induces T-cell leukemia by two distinct pathways","volume":"9","author":"Smith","year":"2014","journal-title":"PLoS One"},{"key":"2025021914460983200_bib59","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.65905","article-title":"Convergent organization of aberrant MYB complex controls oncogenic gene expression in acute myeloid leukemia","volume":"10","author":"Takao","year":"2021","journal-title":"Elife"},{"key":"2025021914460983200_bib60","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1182\/blood.2019001557","article-title":"How I treat newly diagnosed T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma in children","volume":"135","author":"Teachey","year":"2020","journal-title":"Blood"},{"key":"2025021914460983200_bib61","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1182\/blood.V122.21.348.348","article-title":"N-myc is overexpressed in both murine and human early T-cell precursor leukemia and is sufficient to initiate this leukemia in multipotent primitive Arf-\/- thymocytes","volume":"122","author":"Treanor","year":"2013","journal-title":"Blood"},{"key":"2025021914460983200_bib62","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1084\/jem.20122727","article-title":"Interleukin-7 receptor mutants initiate early T cell precursor leukemia in murine thymocyte progenitors with multipotent potential","volume":"211","author":"Treanor","year":"2014","journal-title":"J. Exp. Med."},{"key":"2025021914460983200_bib63","doi-asserted-by":"publisher","first-page":"1173","DOI":"10.1182\/blood-2015-09-668632","article-title":"Targeting acute myeloid leukemia with a small molecule inhibitor of the Myb\/p300 interaction","volume":"127","author":"Uttarkar","year":"2016","journal-title":"Blood"},{"key":"2025021914460983200_bib64","doi-asserted-by":"publisher","first-page":"1276","DOI":"10.1158\/1535-7163.MCT-14-0662","article-title":"Naphthol AS-E phosphate inhibits the activity of the transcription factor Myb by blocking the interaction with the KIX domain of the coactivator p300","volume":"14","author":"Uttarkar","year":"2015","journal-title":"Mol. Cancer Ther."},{"key":"2025021914460983200_bib65","doi-asserted-by":"publisher","first-page":"2905","DOI":"10.1158\/1535-7163.MCT-16-0185","article-title":"Small-molecule disruption of the Myb\/p300 cooperation targets acute myeloid leukemia cells","volume":"15","author":"Uttarkar","year":"2016","journal-title":"Mol. Cancer Ther."},{"key":"2025021914460983200_bib66","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/B978-0-12-391938-0.00004-5","article-title":"4C technology: Protocols and data analysis","volume":"513","author":"Van der Werken","year":"2012","journal-title":"Methods Enzymol."},{"key":"2025021914460983200_bib67","doi-asserted-by":"publisher","first-page":"2571","DOI":"10.1084\/jem.20112239","article-title":"ETV6 mutations in early immature human T cell leukemias","volume":"208","author":"Van Vlierberghe","year":"2011","journal-title":"J. Exp. Med."},{"key":"2025021914460983200_bib68","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/0092-8674(93)80065-M","article-title":"Bcl-2-deficient mice demonstrate fulminant lymphoid apoptosis, polycystic kidneys, and hypopigmented hair","volume":"75","author":"Veis","year":"1993","journal-title":"Cell"},{"key":"2025021914460983200_bib69","doi-asserted-by":"publisher","first-page":"882","DOI":"10.1038\/leu.2017.317","article-title":"Targeting acute myeloid leukemia by drug-induced c-MYB degradation","volume":"32","author":"Walf-Vorderw\u00fclbecke","year":"2018","journal-title":"Leukemia"},{"key":"2025021914460983200_bib70","doi-asserted-by":"publisher","first-page":"1279","DOI":"10.1182\/blood-2018-02-835850","article-title":"Stage-specific roles for Zmiz1 in Notch-dependent steps of early T-cell development","volume":"132","author":"Wang","year":"2018","journal-title":"Blood"},{"key":"2025021914460983200_bib71","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1093\/intimm\/dxq457","article-title":"Immature single-positive CD8+ thymocytes represent the transition from Notch-dependent to Notch-independent T-cell development","volume":"23","author":"Xiong","year":"2011","journal-title":"Int. Immunol."},{"key":"2025021914460983200_bib72","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1038\/s43018-024-00863-5","article-title":"A multiomic atlas identifies a treatment-resistant, bone marrow progenitor-like cell population in T cell acute lymphoblastic leukemia","volume":"6","author":"Xu","year":"2024","journal-title":"Nat. Cancer"},{"key":"2025021914460983200_bib73","doi-asserted-by":"publisher","first-page":"1665","DOI":"10.1101\/gad.1793709","article-title":"Pre-TCR signaling inactivates Notch1 transcription by antagonizing E2A","volume":"23","author":"Yashiro-Ohtani","year":"2009","journal-title":"Genes Dev."},{"key":"2025021914460983200_bib74","doi-asserted-by":"publisher","first-page":"E4946","DOI":"10.1073\/pnas.1407079111","article-title":"Long-range enhancer activity determines Myc sensitivity to Notch inhibitors in T cell leukemia","volume":"111","author":"Yashiro-Ohtani","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025021914460983200_bib75","doi-asserted-by":"publisher","first-page":"1437","DOI":"10.1038\/leu.2012.337","article-title":"Defined, serum-free conditions for in vitro culture of primary human T-ALL blasts","volume":"27","author":"Yost","year":"2013","journal-title":"Leukemia"},{"key":"2025021914460983200_bib76","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1186\/s13059-020-02008-0","article-title":"scATAC-pro: a comprehensive workbench for single-cell chromatin accessibility sequencing data","volume":"21","author":"Yu","year":"2020","journal-title":"Genome Biol."},{"key":"2025021914460983200_bib77","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1038\/nature10725","article-title":"The genetic basis of early T-cell precursor acute lymphoblastic leukaemia","volume":"481","author":"Zhang","year":"2012","journal-title":"Nature"}],"container-title":["Journal of Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/doi\/10.1084\/jem.20231349\/1939160\/jem_20231349.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/doi\/10.1084\/jem.20231349\/1939160\/jem_20231349.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T09:48:01Z","timestamp":1739958481000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/222\/4\/e20231349\/277275\/Native-stem-cell-transcriptional-circuits-define"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,19]]},"references-count":80,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,4,7]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.20231349","relation":{},"ISSN":["0022-1007","1540-9538"],"issn-type":[{"value":"0022-1007","type":"print"},{"value":"1540-9538","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,19]]},"article-number":"e20231349"}}