{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:36:08Z","timestamp":1787027768606,"version":"build-2736575974"},"reference-count":104,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T00:00:00Z","timestamp":1759190400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"QRDI Qatar National Research Funds (QNRF)\u2014National Priority Research Program","award":["NPRP13S-0116-200088"],"award-info":[{"award-number":["NPRP13S-0116-200088"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Wide application of genome sequencing technologies has highlighted extensive genetic diversity in Acute Myeloid Leukemia (AML), yet the specific roles of individual genes remain unclear. This systematic review and meta-analysis aims to provide robust evidence for the prognostic impact of somatic gene mutations in de novo AML patients, while also exploring the prevalence of these mutations. Methods: Eligible studies were identified from PubMed and Scopus, with a focus on those reporting the prognostic influence of somatic gene mutations on overall survival (OS) or relapse-free survival (RFS) when compared to wild-type carriers. We calculated the pooled prevalence with 95% confidence intervals to assess the frequency of these mutations, and the pooled Hazard Ratio (HR) to compare OS and RFS associated with specific gene mutations. Results: We evaluated 53 somatic gene mutations using 80 studies, involving 20,048 de novo AML patients. The analysis revealed that the most prevalent affected genes were NPM1 (27%), DNMT3A (26%), and FLT3-ITD (24%). Mutations in CSF3R, TET2, and TP53 were significantly associated with poorer OS or RFS (p &lt; 0.05). Sensitivity analysis confirmed that ASXL1, DNMT3A, and RUNX1 mutations were consistently linked to inferior OS or RFS. In contrast, CEBPAdm mutations were associated with favorable OS [HR = 0.39 (0.30\u20130.50)] and RFS [HR = 0.44 (0.37\u20130.54)]. Subgroup analysis showed that FLT3-ITD mutations were consistently associated with worse OS or RFS across all subgroups, though no significant subgroup differences were noted. No significant impact on OS or RFS was observed for mutations in GATA2, FLT3-TKD, KRAS, NRAS, IDH1, and IDH2. Conclusions: These findings provide critical insights into AML prognosis, aiding clinical decision-making and improving risk stratification strategies.<\/jats:p>","DOI":"10.3390\/cancers17193189","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T14:16:29Z","timestamp":1759241789000},"page":"3189","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Impact of Somatic Gene Mutations on Prognosis Prediction in De Novo AML: Unraveling Insights from a Systematic Review and Meta-Analysis"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4783-1384","authenticated-orcid":false,"given":"Amal","family":"Elfatih","sequence":"first","affiliation":[{"name":"Genomics and Precision Medicine, College of Health and Life Science, Hamad Bin Khalifa University, Doha 34110, Qatar"},{"name":"Qatar Precision Health Institute, Doha 5825, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nisar","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Genomics and Precision Medicine, College of Health and Life Science, Hamad Bin Khalifa University, Doha 34110, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5585-4455","authenticated-orcid":false,"given":"Luma","family":"Srour","sequence":"additional","affiliation":[{"name":"Genomics and Precision Medicine, College of Health and Life Science, Hamad Bin Khalifa University, Doha 34110, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8983-0929","authenticated-orcid":false,"given":"Idris","family":"Mohammed","sequence":"additional","affiliation":[{"name":"Genomics and Precision Medicine, College of Health and Life Science, Hamad Bin Khalifa University, Doha 34110, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Villiers","sequence":"additional","affiliation":[{"name":"Genomics and Precision Medicine, College of Health and Life Science, Hamad Bin Khalifa University, Doha 34110, Qatar"},{"name":"Department of Medical and Molecular Genetics, King\u2019s College London, London WC2R 2LS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tara","family":"Al-Barazenji","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, College of Health Sciences, Qatar University, Doha 2713, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamdi","family":"Mbarek","sequence":"additional","affiliation":[{"name":"Qatar Precision Health Institute, Doha 5825, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanna","family":"El Akiki","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, College of Health Sciences, Qatar University, Doha 2713, Qatar"},{"name":"Diagnostic Genomic Division, Department of Lab Medicine & Path, Hamad Medical Corporation, Doha 3050, Qatar"},{"name":"Weill Cornell Medicine\u2014Qatar, Qatar Foundation\u2014Education City, Doha 24144, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7747-0930","authenticated-orcid":false,"given":"Puthen Veettil","family":"Jithesh","sequence":"additional","affiliation":[{"name":"Genomics and Precision Medicine, College of Health and Life Science, Hamad Bin Khalifa University, Doha 34110, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Muneer","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery, Hamad Medical Corporation, Doha 3050, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shehab","family":"Fareed","sequence":"additional","affiliation":[{"name":"Hematology Department, NCCCR, Hamad Medical Corporation, Doha 3050, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3429-3094","authenticated-orcid":false,"given":"Borbala","family":"Mifsud","sequence":"additional","affiliation":[{"name":"Genomics and Precision Medicine, College of Health and Life Science, Hamad Bin Khalifa University, Doha 34110, Qatar"},{"name":"William Harvey Research Institute, Queen Mary University London, London WC2A 3JB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1182\/blood-2016-08-733196","article-title":"Diagnosis and Management of AML in Adults: 2017 ELN Recommendations from an International Expert 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