{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T21:36:24Z","timestamp":1793568984952,"version":"4.5.0"},"reference-count":29,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T00:00:00Z","timestamp":1753142400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Genetic alterations in CSF3R, typically associated with chronic neutrophilic leukemia (CNL) and atypical chronic myeloid leukemia (aCML), rarely occur in other myeloid neoplasms. Methods: This study characterized the clinical, morphologic, cytogenetic, and molecular features of 13 patients with non-CNL non-aCML myeloid neoplasms with CSF3R alterations. Patients (median age, 77 years) were categorized into groups with a myelodysplastic\/myeloproliferative neoplasm (MDS\/MPN) (n = 5), acute leukemia (n = 4), and other myeloid neoplasms (n = 4) based on the WHO 2022 and ICC criteria. Results: The CSF3R p.Thr618Ile mutation was most frequent (11\/13), with additional pathogenic variants including p.Gln743Ter and frameshift mutations affecting the cytoplasmic tail. Variant allele frequencies (VAFs) ranged from 2% to 49%, with the highest median VAF in the MDS\/MPN group. Co-mutations varied by subtype; MDS\/MPN, NOS, and CMML cases frequently harbored mutations in epigenetic regulators (ASXL1, TET2) and splicing factors (SF3B1, SRSF2, ZRSR2), while acute leukemia cases showed alterations in JAK3, STAT3, and NRAS. Survival analysis revealed distinct patterns across the three diagnostic groups, with MDS\/MPN having the poorest prognosis. Conclusion: This study expands the recognized spectrum of CSF3R-related myeloid neoplasms and highlights the clinical and molecular heterogeneity associated with these mutations, emphasizing the need for comprehensive molecular profiling and the potential for targeted therapies.<\/jats:p>","DOI":"10.3390\/jcm14155174","type":"journal-article","created":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T08:45:18Z","timestamp":1753173918000},"page":"5174","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Expanding the Spectrum of CSF3R-Mutated Myeloid Neoplasm Beyond Chronic Neutrophilic Leukemia and Atypical Chronic Myeloid Leukemia: A Comprehensive Analysis of 13 Cases"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3299-4201","authenticated-orcid":false,"given":"Neha","family":"Seth","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Donald and Barbara Zucker School of Medicine at Hofstra\/Northwell, Greenvale, NY 11548, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5822-518X","authenticated-orcid":false,"given":"Judith","family":"Brody","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Donald and Barbara Zucker School of Medicine at Hofstra\/Northwell, Greenvale, NY 11548, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peihong","family":"Hsu","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Donald and Barbara Zucker School of Medicine at Hofstra\/Northwell, Greenvale, NY 11548, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Kolitz","sequence":"additional","affiliation":[{"name":"Department of Medicine, Northwell Cancer Institute, Donald and Barbara Zucker School of Medicine at Hofstra\/Northwell, Manhasset, NY 11030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6680-7913","authenticated-orcid":false,"given":"Pratik Q.","family":"Deb","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Donald and Barbara Zucker School of Medicine at Hofstra\/Northwell, Greenvale, NY 11548, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinmin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Donald and Barbara Zucker School of Medicine at Hofstra\/Northwell, Greenvale, NY 11548, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5131","DOI":"10.1182\/blood-2010-01-234120","article-title":"G-CSF and its receptor in myeloid malignancy","volume":"115","author":"Beekman","year":"2010","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/S1074-7613(00)80504-X","article-title":"Impaired production and increased apoptosis of neutrophils in granulocyte colony-stimulating factor receptor-deficient mice","volume":"5","author":"Liu","year":"1996","journal-title":"Immunity"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1847","DOI":"10.1182\/blood-2005-04-1612","article-title":"G-CSF induced reactive oxygen species involves Lyn-PI3-kinase-Akt and contributes to myeloid cell growth","volume":"107","author":"Zhu","year":"2006","journal-title":"Blood"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.bbrc.2019.12.030","article-title":"T618I CSF3R mutations in chronic neutrophilic leukemia induce oncogenic signals through aberrant trafficking and constitutive phosphorylation of the O-glycosylated receptor form","volume":"523","author":"Price","year":"2020","journal-title":"Biochem. 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