{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T15:00:22Z","timestamp":1783090822586,"version":"3.54.6"},"reference-count":76,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T00:00:00Z","timestamp":1755648000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: This study investigates genomic alterations (GA) between NPM1-mutated (NPM1mut) and wild-type (NPM1wt) acute myeloid leukemia (AML), aiming to better understand the AML genomic profile. NPM1mut AML represents a distinct clinical AML subtype with high relapse rates despite initial responsiveness to chemotherapy. Methods: A total of 4206 AML cases from 2019 to 2024 were analyzed using the FoundationOne Heme assay, incorporating comprehensive DNA and RNA sequencing. Patients were stratified into NPM1mut and NPM1wt cohorts, and genomic differences were systematically compared between the two groups. Results: Among 4206 cases, 633 (15.1%) featured NPM1 GA, with over 99% exhibiting short variant mutations. NPM1mut AML was more common in females (53.4% vs. 41.5%) and associated with a slightly higher median age (62 vs. 60 years). GA was more frequent in NPM1mut AML compared to the NPM1wt and included DNMT3A (39.2% vs. 12.6%; p &lt; 0.0001), PTPN11 (18.3% vs. 7.5%; p &lt; 0.0001), FLT3 (54.5% vs. 14.7%; p &lt; 0.0001), IDH1 (16.1% vs. 5.6%; p &lt; 0.0001), IDH2 (19.0% vs. 9.0%; p &lt; 0.0001), TET2 (23.4% vs. 13.5%; p &lt; 0.0001), and WT1 (12.5% vs. 9.4%; p = 0.02). GA was more frequent in NPM1wt AML and included ASXL1 (17.1% vs. 3.6%; p 0.0001), BCOR (7.5% vs. 1.6%; p &lt; 0.0001), KMT2A (14.7% vs. 0.2%; p &lt; 0.0001), RUNX1 (22.5% vs. 1.9%; p 0.0001), STAG2 (6.9% vs. 1.6%; p &lt; 0.0001) and TP53 (19.1% vs. 4.1%; p &lt; 0.0001). Conclusions: Mutations linked to therapy targets in AML, such as (FLT3 and IDH1\/2), PTPN11, and DNMT3A (both associated with inferior outcomes), are more commonly observed in NPM1mut AML, whereas KMT2A, TP53, and myelodysplastic-related mutations are more commonly observed in NPM1wt AML.<\/jats:p>","DOI":"10.3390\/cancers17162710","type":"journal-article","created":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T13:18:14Z","timestamp":1755695894000},"page":"2710","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A Comprehensive Genomic Analysis of Nucleophosmin (NPM1) in Acute Myeloid Leukemia"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8131-2441","authenticated-orcid":false,"given":"Osama","family":"Batayneh","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Hematology\/Oncology, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3065-5759","authenticated-orcid":false,"given":"Mahmoudreza","family":"Moein","sequence":"additional","affiliation":[{"name":"SUNY Upstate Medical University, Syracuse, NY 13210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7518-0921","authenticated-orcid":false,"given":"Alexandra","family":"Goodman","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Hematology\/Oncology, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devashish","family":"Desai","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Hematology\/Oncology, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dean","family":"Pavlick","sequence":"additional","affiliation":[{"name":"Foundation Medicine, Cambridge, MA 02141, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chelsea","family":"Marcus","sequence":"additional","affiliation":[{"name":"Foundation Medicine, Cambridge, MA 02141, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caleb","family":"Ho","sequence":"additional","affiliation":[{"name":"Foundation Medicine, Cambridge, MA 02141, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell","family":"Madison","sequence":"additional","affiliation":[{"name":"Foundation Medicine, Cambridge, MA 02141, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard S. P.","family":"Huang","sequence":"additional","affiliation":[{"name":"Foundation Medicine, Cambridge, MA 02141, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8494-2596","authenticated-orcid":false,"given":"Jeffrey S.","family":"Ross","sequence":"additional","affiliation":[{"name":"SUNY Upstate Medical University, Syracuse, NY 13210, USA"},{"name":"Foundation Medicine, Cambridge, MA 02141, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3420-0601","authenticated-orcid":false,"given":"Teresa","family":"Gentile","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Hematology\/Oncology, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Hematology\/Oncology, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishna Bilas","family":"Ghimire","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Hematology\/Oncology, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e2300229","DOI":"10.1200\/GO.23.00229","article-title":"Burden of AML, 1990\u20132019: Estimates From the Global Burden of Disease Study","volume":"9","author":"Jani","year":"2023","journal-title":"JCO Glob. 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