{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T23:40:40Z","timestamp":1787614840766,"version":"build-2736575974"},"reference-count":39,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T00:00:00Z","timestamp":1770681600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Acute myeloid leukemia (AML) is genomically heterogeneous, and translating baseline molecular data into individualized prognosis remains difficult. We assessed real-world outcomes and externally validated the Sanger Institute AML multistage prognostic model. Methods: This single-center, retrospective study included 73 AML patients who underwent targeted NGS profiling. In intensively treated patients, the published, validated Sanger AML multistage prognostic model was compared with observed 12- and 36-month clinical outcomes using quadratic-weighted Cohen\u2019s kappa. Results: Median age was 61 years, and median overall survival was 13 months, with the most significant survival differences driven by treatment intensity. TP53 mutations occurred in 7 patients (9.6%) and were linked to primary refractoriness and extremely poor survival. TP53 was the only independent predictor of death (HR 8.07, 95% CI 2.23\u201329.13; p = 0.0014). Model concordance was moderate at 12 months (29 evaluable cases; weighted \u03ba = 0.52; alive\/dead \u03ba = 0.52) and fair-to-moderate at 36 months (23 cases; weighted \u03ba = 0.46). The tool performed best for predicted death without remission, while most discrepancies involved patients expected to remain in first remission who later relapsed and died. Conclusions: TP53 disruption dominates prognosis in real-world AML. The multistage tool supports early high-risk identification but shows limited long-term calibration, motivating the development of dynamic models integrating contemporary therapies and longitudinal min\/serial NGS data.<\/jats:p>","DOI":"10.3390\/genes17020218","type":"journal-article","created":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T12:07:06Z","timestamp":1770725226000},"page":"218","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Integrating Genomic and Clinical Data in AML: Real-World Application of the Sanger Multistage Model"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9510-4755","authenticated-orcid":false,"given":"Andrea","family":"Duminuco","sequence":"first","affiliation":[{"name":"Hematology with BMT Unit, A.O.U. Policlinico \u201cG. Rodolico-S. Marco\u201d, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7948-3580","authenticated-orcid":false,"given":"Silvia Rita","family":"Vitale","sequence":"additional","affiliation":[{"name":"Center of Experimental Oncology and Hematology, A.O.U. Policlinico \u201cG. Rodolico-S. Marco\u201d, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Nardo","sequence":"additional","affiliation":[{"name":"Hematology with BMT Unit, A.O.U. Policlinico \u201cG. Rodolico-S. Marco\u201d, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5704-466X","authenticated-orcid":false,"given":"Patrick","family":"Harrington","sequence":"additional","affiliation":[{"name":"Department of Haematology, Guy\u2019s and St Thomas\u2019 NHS Foundation Trust, London SE1 9RT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Stella","sequence":"additional","affiliation":[{"name":"Center of Experimental Oncology and Hematology, A.O.U. Policlinico \u201cG. Rodolico-S. Marco\u201d, 95123 Catania, Italy"},{"name":"Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5896-8573","authenticated-orcid":false,"given":"Michele","family":"Massimino","sequence":"additional","affiliation":[{"name":"Center of Experimental Oncology and Hematology, A.O.U. Policlinico \u201cG. Rodolico-S. Marco\u201d, 95123 Catania, Italy"},{"name":"Department of General Surgery and Medical-Surgical Specialties, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1044-1008","authenticated-orcid":false,"given":"Cristina","family":"Tomarchio","sequence":"additional","affiliation":[{"name":"Center of Experimental Oncology and Hematology, A.O.U. Policlinico \u201cG. Rodolico-S. Marco\u201d, 95123 Catania, Italy"},{"name":"Department of Precision Medicine in Medical, Surgical and Critical Care (Me.Pre.C.C.), University of Palermo, 90128 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Mauro","sequence":"additional","affiliation":[{"name":"Hematology with BMT Unit, A.O.U. Policlinico \u201cG. Rodolico-S. Marco\u201d, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina S.","family":"Parisi","sequence":"additional","affiliation":[{"name":"Hematology with BMT Unit, A.O.U. Policlinico \u201cG. Rodolico-S. Marco\u201d, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cinzia","family":"Maugeri","sequence":"additional","affiliation":[{"name":"Hematology with BMT Unit, A.O.U. Policlinico \u201cG. Rodolico-S. Marco\u201d, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Di Raimondo","sequence":"additional","affiliation":[{"name":"Hematology with BMT Unit, A.O.U. Policlinico \u201cG. Rodolico-S. Marco\u201d, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1859-6319","authenticated-orcid":false,"given":"Giuseppe A.","family":"Palumbo","sequence":"additional","affiliation":[{"name":"Hematology with BMT Unit, A.O.U. Policlinico \u201cG. Rodolico-S. Marco\u201d, 95123 Catania, Italy"},{"name":"Department of Medical Surgical Sciences and Advanced Technologies \u201cG.F. Ingrassia\u201d, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Livia","family":"Manzella","sequence":"additional","affiliation":[{"name":"Center of Experimental Oncology and Hematology, A.O.U. Policlinico \u201cG. Rodolico-S. Marco\u201d, 95123 Catania, Italy"},{"name":"Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1922-5157","authenticated-orcid":false,"given":"Calogero","family":"Vetro","sequence":"additional","affiliation":[{"name":"Hematology and Bone Marrow Transplantation Unit, Hospital of Bolzano (SABES-Azienda Sanitaria dell\u2019 Alto Adige), Teaching Hospital of Paracelsus Medical University, 39100 Bolzano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4622","DOI":"10.1038\/s41467-022-32103-8","article-title":"Unified Classification and Risk-Stratification in Acute Myeloid Leukemia","volume":"13","author":"Tazi","year":"2022","journal-title":"Nat. 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