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Leukemia is frequently associated with aberrant\n                  <jats:italic>HOXA<\/jats:italic>\n                  expression driven by translocations in nucleoporin genes or\n                  <jats:italic>KMT2A<\/jats:italic>\n                  , and mutations in\n                  <jats:italic>NPM1<\/jats:italic>\n                  . How disparate mutations converge on this regulatory pathway is not understood. Here we demonstrate that mutant NPM1 (NPM1c) forms nuclear condensates in multiple human cell lines, mouse models, and primary patient samples. We show NPM1c phase separation is necessary and sufficient to coordinate the recruitment of NUP98 and KMT2A to condensates. Through extensive mutagenesis and pharmacological destabilization of phase separation, we find that NPM1c condensates are necessary for regulating gene expression, promoting\n                  <jats:italic>in vivo<\/jats:italic>\n                  expansion, and maintaining the undifferentiated leukemic state. Finally, we show that nucleoporin and KMT2A fusion proteins form condensates that are biophysically indistinguishable from NPM1c condensates. Together, these data define a new condensate underlying leukemias that we term coordinating bodies (C-bodies), and propose C-bodies as a therapeutic vulnerability.\n                <\/jats:p>","DOI":"10.1101\/2025.05.23.655671","type":"posted-content","created":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T17:09:41Z","timestamp":1748452181000},"source":"Crossref","is-referenced-by-count":2,"title":["Nuclear Phase Separation Drives NPM1-mutant Acute Myeloid Leukemia"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8982-1475","authenticated-orcid":false,"given":"Gandhar K.","family":"Datar","sequence":"first","affiliation":[{"name":"Medical Scientist Training Program, Baylor College of Medicine, Houston, TX, USA"},{"name":"Cancer and Cell Biology Graduate Program, Baylor College of Medicine, Houston, TX, USA"},{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA"},{"name":"Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elmira","family":"Khabusheva","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA"},{"name":"Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Archish","family":"Anand","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Beale","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA"},{"name":"Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwa","family":"Sadek","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA"},{"name":"Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, TX, USA"},{"name":"Diagnostic Genetics and Genomics Program, School of Health Professions, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Wei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA"},{"name":"Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evdokiia","family":"Potolitsyna","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nayara","family":"Alcantara-Contessoto","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangyuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA"},{"name":"Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josephine","family":"De La Fuente","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA"},{"name":"Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Dollinger","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Guzman","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA"},{"name":"Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandra","family":"Martell","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA"},{"name":"Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Wohlan","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA"},{"name":"Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhishek","family":"Maiti","sequence":"additional","affiliation":[{"name":"Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas J.","family":"Short","sequence":"additional","affiliation":[{"name":"Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. Stephen","family":"Yi","sequence":"additional","affiliation":[{"name":"Baylor Research Institute and Baylor College of Medicine, Temple, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vibeke","family":"Andresen","sequence":"additional","affiliation":[{"name":"K.G. Jebsen Centre for Myeloid Blood Cancer, Department of Clinical Science, University of Bergen, Bergen, Norway"},{"name":"Centre of Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bj\u00f8rn Tore","family":"Gjertsen","sequence":"additional","affiliation":[{"name":"K.G. Jebsen Centre for Myeloid Blood Cancer, Department of Clinical Science, University of Bergen, Bergen, Norway"},{"name":"Centre of Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, Bergen, Norway"},{"name":"Department of Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brunangelo","family":"Falini","sequence":"additional","affiliation":[{"name":"Institute of Hematology and Center for Hemato-Oncological research (CREO), University of Perugia and Santa Maria della Misericordia Hospital, Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel E.","family":"Rau","sequence":"additional","affiliation":[{"name":"Ben Towne Center for Childhood Cancer Research, Seattle Children\u2019s Research Institute, Department of Pediatrics, University of Washington School of Medicine, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Brunetti","sequence":"additional","affiliation":[{"name":"Department of Molecular and Clinical Sciences, Universit\u00e0 Politecnica delle Marche, Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nidhi","family":"Sahni","sequence":"additional","affiliation":[{"name":"Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"},{"name":"Quantitative and Computational Biosciences Program, Baylor College of Medicine, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1111-2932","authenticated-orcid":false,"given":"Margaret A.","family":"Goodell","sequence":"additional","affiliation":[{"name":"Medical Scientist Training Program, Baylor College of Medicine, Houston, TX, USA"},{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA"},{"name":"Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1516-4484","authenticated-orcid":false,"given":"Joshua A.","family":"Riback","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026041123420654000_2025.05.23.655671v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-020-00303-z"},{"key":"2026041123420654000_2025.05.23.655671v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1885"},{"key":"2026041123420654000_2025.05.23.655671v1.3","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.13571"},{"key":"2026041123420654000_2025.05.23.655671v1.4","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/195209"},{"key":"2026041123420654000_2025.05.23.655671v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2009.473"},{"key":"2026041123420654000_2025.05.23.655671v1.6","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13599"},{"key":"2026041123420654000_2025.05.23.655671v1.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2014.03.006"},{"key":"2026041123420654000_2025.05.23.655671v1.8","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1994.tb06356.x"},{"key":"2026041123420654000_2025.05.23.655671v1.9","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201112044"},{"key":"2026041123420654000_2025.05.23.655671v1.10","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2017.7"},{"key":"2026041123420654000_2025.05.23.655671v1.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.02.007"},{"key":"2026041123420654000_2025.05.23.655671v1.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2020.03.018"},{"key":"2026041123420654000_2025.05.23.655671v1.13","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-39102-9"},{"key":"2026041123420654000_2025.05.23.655671v1.14","first-page":"4080","article-title":"Hotspot mutations in the structured ENL YEATS domain link aberrant transcriptional condensates and cancer","volume":"0","year":"2022","journal-title":"Mol. 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