{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T17:57:04Z","timestamp":1785607024897,"version":"3.56.0"},"posted":{"date-parts":[[2026,7,29]]},"group-title":"Cancer Biology","reference-count":20,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["K08CA252883"],"award-info":[{"award-number":["K08CA252883"]}],"id":[{"id":"https:\/\/ror.org\/040gcmg81","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","award":["R01HD093826"],"award-info":[{"award-number":["R01HD093826"]}]},{"award":["R01HL165119."],"award-info":[{"award-number":["R01HL165119."]}],"id":[{"id":"https:\/\/ror.org\/023ny1p48","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Chronic myelomonocytic leukemia (CMML) is an aggressive hematologic malignancy characterized by excess inflammatory signaling and clonal myeloproliferation. The relative contribution of neutrophils (PMNs) to the inflammatory milieu in CMML is poorly understood. In this study we sought to understand whether neutrophil extracellular trap (NET) formation, a key mediator of neutrophilic inflammation, is dysregulated in CMML and can be therapeutically targeted with a novel peptide inhibitor of NETosis called neonatal NET-inhibitory factor (nNIF). Here, we demonstrate that baseline NET formation is aberrantly increased in primary CMML PMNs transcriptionally primed for NETosis, and that soluble factors produced during CMML NET formation promote clonogenicity in CMML CD34\n                  <jats:sup>+<\/jats:sup>\n                  hematopoietic cells matched to the same patient. Further, we show that nNIF and clinical agents under investigation in CMML effectively inhibit NETosis, warranting further study of NET inhibitory agents in this rare disease with limited treatment options.\n                <\/jats:p>","DOI":"10.64898\/2026.07.28.741351","type":"posted-content","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T14:45:20Z","timestamp":1785336320000},"source":"Crossref","is-referenced-by-count":0,"title":["Dysregulated neutrophil extracellular trap formation is a novel driver of clonogenicity and therapeutic vulnerability in CMML"],"prefix":"10.64898","author":[{"given":"Saveg","family":"Yadav","sequence":"first","affiliation":[{"name":"Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Callie T.","family":"Brown","sequence":"additional","affiliation":[{"name":"Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Cody","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Neonatology, University of Utah, Salt Lake City, Utah, USA"},{"name":"Molecular Medicine Program, University of Utah, Salt Lake City, Utah, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William L.","family":"Heaton","sequence":"additional","affiliation":[{"name":"Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"de Araujo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Neonatology, University of Utah, Salt Lake City, Utah, USA"},{"name":"Molecular Medicine Program, University of Utah, Salt Lake City, Utah, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Marchetti","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Immunology, Inflammation and Infections Disease Initiative-Utah Center for Genetic Discovery Bioinformatics Core, University of Utah, Salt Lake City, UT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Campbell","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Washington University in St. Louis, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony D.","family":"Pomicter","sequence":"additional","affiliation":[{"name":"Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA"},{"name":"Department of Internal Medicine, Division of Hematology and Hematologic Malignancies University of Utah, Salt Lake City, Utah, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"Williams","sequence":"additional","affiliation":[{"name":"Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian Con","family":"Yost","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Neonatology, University of Utah, Salt Lake City, Utah, USA"},{"name":"Molecular Medicine Program, University of Utah, Salt Lake City, Utah, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon E.","family":"Elf","sequence":"additional","affiliation":[{"name":"Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA"},{"name":"Department of Internal Medicine, Division of Hematology and Hematologic Malignancies University of Utah, Salt Lake City, Utah, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5374-3831","authenticated-orcid":false,"given":"Ami B.","family":"Patel","sequence":"additional","affiliation":[{"name":"Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA"},{"name":"Department of Internal Medicine, Division of Hematology and Hematologic Malignancies University of Utah, Salt Lake City, Utah, 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