{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T17:53:27Z","timestamp":1792173207318,"version":"4.4.0"},"reference-count":0,"publisher":"American Society of Hematology","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:p>RAS mutations are recurrent in acute myeloid leukemia (AML); yet, their genomic and clinical landscape remain poorly characterized. We analyzed centralized molecular profiling data in 8,553 patients with newly diagnosed AML. Of these, 1,775 (21%) harbored RAS mutations: NRAS in 1,103 (13%), KRAS in 445 (5%), and both in 227 (3%). RAS mutations primarily clustered in P-loop hotspots (G12\/G13, 70%), with NRAS showing higher Q61 mutation prevalence (24% vs. 9%) and KRAS showing additional K117\/A146 hotspots. Multiple RAS mutations occurred in 23% of patients. Convergent evolution of RAS signaling mutations emerged as a key feature of RASmut AML. RTK\/RAS pathway mutations were non-uniformly enriched: PTPN11, KIT and FLT3-TKD mutations were positively associated, CBL mutations showed no association, and FLT3-ITD mutations were negatively associated. The prognostic impact of RAS mutations was dependent on the genomic background and treatment. In multivariate analyses in intensively treated patients, NRAS mutations showed opposing associations with overall survival (OS): adverse in patients with AML, myelodysplasia-related (HR=1.32, p=0.036) and favorable in those with NPM1 (HR=0.61, p=0.036) or FLT3-ITD (HR=0.63, p=0.048) mutations, among others. KRAS mutations predicted inferior OS (HR=1.41; p=0.003). In patients treated with non-intensive, venetoclax-based regimens, RAS mutations were associated with markedly inferior OS in patients with NPM1 (HR=2.98, p=0.007) or IDH1\/2 mutations (HR=4.06, p&amp;lt;0.001). These data inform risk stratification and development of RAS-targeting strategies in AML.<\/jats:p>","DOI":"10.1182\/blood.2026033409","type":"journal-article","created":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T17:22:55Z","timestamp":1792171375000},"update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":0,"title":["Genomic and clinical landscape of RAS mutations in acute myeloid leukemia"],"prefix":"10.1182","author":[{"given":"Eduardo","family":"Rodr\u00edguez-Arbol\u00ed","sequence":"first","affiliation":[{"name":"Department of Hematology, Hospital Universitario Virgen del Roc\u00edo, Instituto de Biomedicina de Sevilla (IBIS\/CSIC), University of Seville, Sevilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Soria-Saldise","sequence":"additional","affiliation":[{"name":"Hospital Universitario Virgen del Rocio, Instituto de Biomedicina de Sevilla (IBIS \/ CISC \/ CIBERON), Sevilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6735-0038","authenticated-orcid":false,"given":"Eva","family":"Barragan","sequence":"additional","affiliation":[{"name":"Hospital La Fe, Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Ayala","sequence":"additional","affiliation":[{"name":"HOSPITAL 12 DE OCTUBRE, MADRID, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joaquin","family":"S\u00e1nchez-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Hospital Universitario Reina Sof\u00eda (HURS); Instituto Maim\u00f3nides de Investigaci\u00f3n Biom\u00e9dica de C\u00f3rdoba (IMIBIC), Universidad de C\u00f3rdoba (UCO), C\u00f3rdoba, C\u00f3rdoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4796-1445","authenticated-orcid":false,"given":"Cristina","family":"Bilbao-Sieyro","sequence":"additional","affiliation":[{"name":"Hospital Universitario de Gran Canaria Dr. Negr\u00edn, Instituto de Investigaci\u00f3n Sanitaria de Canarias (IISC), Las Palmas De Gran Canaria, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1624-6059","authenticated-orcid":false,"given":"M. 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