{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T04:54:49Z","timestamp":1790916889465,"version":"4.1.0"},"reference-count":82,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T00:00:00Z","timestamp":1738022400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Benzene, a well-known carcinogenic airborne pollutant, poses significant health risks, particularly in industries such as petroleum, shoemaking, and painting. Despite strict regulations, chronic occupational exposure persists, contributing to the onset of acute myeloid leukemia (AML) and other malignancies. Benzene\u2019s carcinogenicity stems from its metabolic activation, leading to increased oxidative stress, DNA damage, and cancer transformation. While its toxicity is well-documented, the link between genetic and epigenetic alterations and cancer susceptibility in exposed workers remains underexplored. This study aims to identify early biomarkers of benzene exposure and AML risk by analyzing gene expression and DNA methylation datasets from GEO DataSets, integrated with molecular pathway analyses, as well as miRNA-target and protein-protein network evaluations. This multi-approach led to the identification of nine deregulated genes (CRK, CXCR6, GSPT1, KPNA1, MECP2, MELTF, NFKB1, TBC1D7, ZNF331) in workers exposed to benzene, with NFKB1 showing strong discriminatory potential. Also, dose-dependent DNA methylation changes were observed in CXCR6 and MELTF, while selected miRNAs such as let-7d-5p, miR-126-3p, and miR-361-5p emerged as key post-transcriptional regulators. Furthermore, functional enrichment linked these genes to immune response, inflammation, cell proliferation, and apoptosis pathways. While network analyses highlighted NFKB1, CRK, and CXCR6 as central to benzene-associated leukemogenesis. Altogether, these findings provide novel insights into an early biomarker fingerprint for benzene exposure and AML susceptibility, supporting the future development of biomolecular-based targeted occupational health monitoring and personalized preventive strategies for at-risk workers.<\/jats:p>","DOI":"10.3390\/ijms26031138","type":"journal-article","created":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T06:47:29Z","timestamp":1738046849000},"page":"1138","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Integrated Computational Analysis Reveals Early Genetic and Epigenetic AML Susceptibility Biomarkers in Benzene-Exposed Workers"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9363-6523","authenticated-orcid":false,"given":"Silvia","family":"Vivarelli","sequence":"first","affiliation":[{"name":"Department of Biomedical and Dental Sciences, Morphological and Functional Imaging, Section of Occupational Medicine, University of Messina, 98124 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0575-3090","authenticated-orcid":false,"given":"Cigdem","family":"Sevim","sequence":"additional","affiliation":[{"name":"Department of Medical Pharmacology, Faculty of Medicine, Kastamonu University, Kastamonu 37150, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3033-627X","authenticated-orcid":false,"given":"Federica","family":"Giamb\u00f2","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Dental Sciences, Morphological and Functional Imaging, Section of Occupational Medicine, University of Messina, 98124 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6369-2700","authenticated-orcid":false,"given":"Concettina","family":"Fenga","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Dental Sciences, Morphological and Functional Imaging, Section of Occupational Medicine, University of Messina, 98124 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.1016\/S1470-2045(17)30832-X","article-title":"Carcinogenicity of benzene","volume":"18","author":"Loomis","year":"2017","journal-title":"Lancet Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1164\/rccm.202308-1440OC","article-title":"Long-Term Exposure to Low Concentrations of Ambient Benzene and Mortality in a National English Cohort","volume":"209","author":"Wang","year":"2024","journal-title":"Am. 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