{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T15:18:53Z","timestamp":1786115933372,"version":"build-2736575974"},"posted":{"date-parts":[[2026,8,4]]},"group-title":"Cancer Biology","reference-count":28,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["R01 CA293588-01"],"award-info":[{"award-number":["R01 CA293588-01"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,8,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Leukemic stem cells (LSCs) play a central role in disease progression, therapeutic resistance, and relapse in acute myeloid leukemia (AML). However, the identification and characterization of LSCs remain challenging because of their low abundance and their close phenotypic resemblance to normal hematopoietic stem and progenitor cells. Although patient-derived xenograft (PDX) models have provided important insights into AML biology and LSC heterogeneity, the relative engraftment potential of distinct\n                  <jats:italic>CEBPA<\/jats:italic>\n                  mutation subtypes and the immunophenotypic identity of LSCs in\n                  <jats:italic>CEBPA<\/jats:italic>\n                  N-terminal mutant AML (\n                  <jats:italic>CEBPA<\/jats:italic>\n                  -\n                  <jats:italic>N<\/jats:italic>\n                  -AML) remain poorly defined. To address these questions, we compared the engraftment characteristics of primary human CEBPA-mutated AML samples representing the major mutational subtypes using the highly permissive NSGS xenograft model. Primary\n                  <jats:italic>CEBPA<\/jats:italic>\n                  -N-AML samples exhibited markedly greater engraftment efficiency and leukemogenic potential than other\n                  <jats:italic>CEBPA<\/jats:italic>\n                  -mutated AML subtypes. Furthermore, we identified a CD366\u207aCD73\u207aCD123\u207aCD117\u207aCD371\u207aCD247\u207a cell population that is highly enriched for functional LSCs in\n                  <jats:italic>CEBPA-N<\/jats:italic>\n                  -AML, demonstrating enhanced clonogenic activity, leukemia-initiating capacity, and long-term self-renewal. Collectively, our findings demonstrate that the leukemogenic potential of\n                  <jats:italic>CEBPA<\/jats:italic>\n                  -mutated AML is strongly influenced by mutation subtype, with\n                  <jats:italic>CEBPA-N<\/jats:italic>\n                  -AML exhibiting superior leukemia-propagating capacity in vivo. We further define a novel immunophenotypic LSC signature specific to\n                  <jats:italic>CEBPA-N<\/jats:italic>\n                  -AML, providing new insights into LSC heterogeneity in\n                  <jats:italic>CEBPA<\/jats:italic>\n                  -mutated AML and establishing a foundation for the development of LSC-directed therapeutic strategies.\n                <\/jats:p>","DOI":"10.64898\/2026.08.03.742558","type":"posted-content","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T16:55:47Z","timestamp":1785862547000},"source":"Crossref","is-referenced-by-count":0,"title":["Human\n                  <i>CEBPA<\/i>\n                  -N AML exhibits enhanced engraftment and a C\/EBP\n                  <i>\u03b1<\/i>\n                  -p30-driven leukemic stem cell program"],"prefix":"10.64898","author":[{"given":"Philomina Sona","family":"Peramangalam","sequence":"first","affiliation":[{"name":"Program in Hematopoiesis and Immunology, Versiti Blood Research Institute, Milwaukee, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayuresh","family":"Konde","sequence":"additional","affiliation":[{"name":"Program in Hematopoiesis and Immunology, Versiti Blood Research Institute, Milwaukee, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Onur","family":"Karakaslar","sequence":"additional","affiliation":[{"name":"Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Wolf","sequence":"additional","affiliation":[{"name":"Department of Medicine, Hematology and Oncology, University Hospital, Goethe University Frankfurt, Frankfurt am Main, Germany"},{"name":"German Cancer Consortium (DKTK), partner site Frankfurt\/Mainz, a partnership between DKFZ and UCT Frankfurt-Marburg, Germany, Frankfurt am Main, Germany"},{"name":"Frankfurt Cancer Institute (FCI), Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shikan","family":"Zheng","sequence":"additional","affiliation":[{"name":"Program in Hematopoiesis and Immunology, Versiti Blood Research Institute, Milwaukee, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akmal","family":"Salimov","sequence":"additional","affiliation":[{"name":"Division of Hematology & Oncology, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sridevi","family":"Surapally","sequence":"additional","affiliation":[{"name":"Program in Hematopoiesis and Immunology, Versiti Blood Research Institute, Milwaukee, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marieke","family":"Griffioen","sequence":"additional","affiliation":[{"name":"Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tongjun","family":"Gu","sequence":"additional","affiliation":[{"name":"Program in Hematopoiesis and Immunology, Versiti Blood Research Institute, Milwaukee, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sridhar","family":"Rao","sequence":"additional","affiliation":[{"name":"Program in Hematopoiesis and Immunology, Versiti Blood Research Institute, Milwaukee, WI"},{"name":"Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI"},{"name":"Department of Pediatrics, Division of Hematology, Oncology, and Transplantation, Medical College of Wisconsin, Milwaukee, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel G","family":"Tenen","sequence":"additional","affiliation":[{"name":"Harvard Stem Cell Institute, Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Oellerich","sequence":"additional","affiliation":[{"name":"Department of Medicine, Hematology and Oncology, University Hospital, Goethe University Frankfurt, Frankfurt am Main, Germany"},{"name":"German Cancer Consortium (DKTK), partner site Frankfurt\/Mainz, a partnership between DKFZ and UCT Frankfurt-Marburg, Germany, Frankfurt am Main, Germany"},{"name":"Frankfurt Cancer Institute (FCI), Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"van den Akker","sequence":"additional","affiliation":[{"name":"Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Carroll","sequence":"additional","affiliation":[{"name":"Division of Hematology & Oncology, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caner","family":"Saygin","sequence":"additional","affiliation":[{"name":"Section of Hematology\/Oncology, University of Chicago, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A.","family":"Pulikkan","sequence":"additional","affiliation":[{"name":"Program in Hematopoiesis and Immunology, Versiti Blood Research Institute, Milwaukee, WI"},{"name":"Frankfurt Cancer Institute (FCI), Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026080523301119000_2026.08.03.742558v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2004.11.006"},{"key":"2026080523301119000_2026.08.03.742558v1.2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.20.9606"},{"key":"2026080523301119000_2026.08.03.742558v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/85820"},{"key":"2026080523301119000_2026.08.03.742558v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-024-02140-x"},{"key":"2026080523301119000_2026.08.03.742558v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2017.229"},{"key":"2026080523301119000_2026.08.03.742558v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2008.02.008"},{"key":"2026080523301119000_2026.08.03.742558v1.7","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020009680"},{"key":"2026080523301119000_2026.08.03.742558v1.8","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-29304-6"},{"key":"2026080523301119000_2026.08.03.742558v1.9","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-10-696054"},{"key":"2026080523301119000_2026.08.03.742558v1.10","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0209034"},{"key":"2026080523301119000_2026.08.03.742558v1.11","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-024-02137-6"},{"key":"2026080523301119000_2026.08.03.742558v1.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2022.02.006"},{"key":"2026080523301119000_2026.08.03.742558v1.13","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2017.183202"},{"key":"2026080523301119000_2026.08.03.742558v1.14","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2025018002"},{"key":"2026080523301119000_2026.08.03.742558v1.15","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2020003958"},{"key":"2026080523301119000_2026.08.03.742558v1.16","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19119-8"},{"key":"2026080523301119000_2026.08.03.742558v1.17","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-024-02358-9"},{"key":"2026080523301119000_2026.08.03.742558v1.18","doi-asserted-by":"publisher","DOI":"10.1038\/nature20598"},{"key":"2026080523301119000_2026.08.03.742558v1.19","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aaw4304"},{"key":"2026080523301119000_2026.08.03.742558v1.20","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1100551108"},{"key":"2026080523301119000_2026.08.03.742558v1.21","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2017.09.004"},{"key":"2026080523301119000_2026.08.03.742558v1.22","doi-asserted-by":"publisher","DOI":"10.1111\/ijlh.14124"},{"key":"2026080523301119000_2026.08.03.742558v1.23","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2016.151910"},{"key":"2026080523301119000_2026.08.03.742558v1.24","doi-asserted-by":"publisher","DOI":"10.1038\/367645a0"},{"key":"2026080523301119000_2026.08.03.742558v1.25","doi-asserted-by":"publisher","DOI":"10.1038\/nm0797-730"},{"key":"2026080523301119000_2026.08.03.742558v1.26","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2009.04.018"},{"key":"2026080523301119000_2026.08.03.742558v1.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2015.08.008"},{"key":"2026080523301119000_2026.08.03.742558v1.28","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-11-683649"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.08.03.742558","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T06:30:18Z","timestamp":1785997818000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.08.03.742558"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,4]]},"references-count":28,"URL":"https:\/\/doi.org\/10.64898\/2026.08.03.742558","relation":{},"subject":[],"published":{"date-parts":[[2026,8,4]]},"subtype":"preprint"}}