{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T10:08:05Z","timestamp":1767262085264,"version":"build-2065373602"},"reference-count":37,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T00:00:00Z","timestamp":1748908800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Penn State Health Children\u2019s Hospital Four Diamonds Funds"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background: While adult and pediatric acute myeloid leukemia (AML) exhibit genetic distinctions, investigating their common gene expression program is critical for understanding the fundamental biological mechanisms that drive diverse cellular responses. However, existing gene signatures, predominantly tailored for overall survival (OS), may not adequately forecast event-free survival (EFS). EFS represents the time patients survive without disease recurrence, progression, or further treatment, a crucial metric for evaluating drug efficacy and assessing the clinical benefits of treatment. Methods: We performed an integrated analysis of adult TCGA and pediatric TARGET expression datasets to pinpoint genes and pathways associated with EFS in both adult and pediatric AML. Additionally, we constructed a predictive model using one dataset and validated it on the other to unveil a novel gene signature. Results: A five-gene signature comprising F2RL3, IL2RA, MYH15, SIX3, and SOBP was identified for EFS for both adult and pediatric AML. The test Area Under the ROC Curves (AUCs) for the 2-year and 5-year cutoffs of adult TCGA data were 0.851 (95% CI (Confidence Interval): 0.778\u20130.923) and 0.848 (95% CI: 0.729\u20130.968), respectively. Similarly, the test AUCs for the 2-year and 5-year cutoffs of Pediatric TARGET data were 0.725 (95% CI: 0.640\u20130.811) and 0.695 (95% CI: 0.59\u20130.80), respectively. When patients were stratified into three equal-sized prognostic subtypes based on the five-gene test risk scores, the P-values of tertile partitions for TARGET and TCGA data were 2.32e\u22126 and 5.12e\u221214, respectively, indicating superior performance compared to cytogenetic risk stratification within the same data (TARGET: P = 0.0019; TCGA: P = 0.0086). Despite being identified for EFS, the five-gene signature successfully stratified patients into distinct OS groups across two additional independent datasets. Conclusions: This five-gene signature demonstrates robust performance in both EFS and OS risk prediction and might be clinically significant.<\/jats:p>","DOI":"10.3390\/diagnostics15111421","type":"journal-article","created":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T11:55:52Z","timestamp":1748951752000},"page":"1421","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Five-Gene Signature for the Prediction of Event-Free Survival of Both Pediatric and Adult Acute Myeloid Leukemia"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5787-3441","authenticated-orcid":false,"given":"Dechang","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alvin J.","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cognitive Science, Case Western Reserve University, Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9030-3253","authenticated-orcid":false,"given":"Li","family":"Sheng","sequence":"additional","affiliation":[{"name":"Department of Mathematics, Drexel University, Philadelphia, PA 19104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenqiu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Statistics, Radiation Effects Research Foundation, Hiroshima 732-0815, Japan"},{"name":"Division of Pediatric Hematology and Oncology, Department of Pediatrics, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3992-2817","authenticated-orcid":false,"given":"Irina","family":"Elcheva","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology and Oncology, Department of Pediatrics, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1038\/nm.4439","article-title":"The molecular landscape of pediatric acute myeloid leukemia reveals recurrent structural alterations and age-specific mutational interactions","volume":"24","author":"Bolouri","year":"2018","journal-title":"Nat. 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