{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T11:05:50Z","timestamp":1768215950955,"version":"3.49.0"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T00:00:00Z","timestamp":1768176000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"\n Background<\/jats:title>\n \n Aberrant expression of Homeobox (\n HOX<\/jats:italic>\n ) genes has been observed in acute myeloid leukemia (AML), but their epigenetic regulatory mechanisms remain largely elusive. Previously, we identified\n HOXA9<\/jats:italic>\n hypomethylation, among\n HOXA<\/jats:italic>\n family genes as an epigenetic biomarker for predicting clinical outcomes and guiding treatment choices in AML. Herein, we further investigated the methylation of\n HOXB<\/jats:italic>\n family members in AML and determined its clinical implications.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We first systematically analyzed the association of\n HOXB<\/jats:italic>\n methylation with expression and clinical outcomes in AML from The Cancer Genome Atlas (TCGA) database. Next, the candidate prognosis-related gene\n HOXB3<\/jats:italic>\n was selected for clinical relevance analysis and further verified in another independent cohort from our hospital.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Hypomethylation of\n HOXB3<\/jats:italic>\n , which was negatively associated with its expression, was correlated with adverse prognosis among\n HOXB<\/jats:italic>\n family genes in AML from TCGA datasets. Clinically, AML patients with\n HOXB3<\/jats:italic>\n hypomethylation had unique clinical subtypes and cytogenetic\/molecular patterns, including FAB-M5, normal karyotype, cytogenetic\/molecular-intermediate risks, and mutations in\n FLT3<\/jats:italic>\n -ITD,\n NPM1<\/jats:italic>\n and\n DNMT3A<\/jats:italic>\n . Despite these associations,\n HOXB3<\/jats:italic>\n hypomethylation was an independent prognostic biomarker for AML. Bioinformatics analysis demonstrated the association of\n HOXB3<\/jats:italic>\n hypomethylation with several leukemia-related genes (\n HOXB<\/jats:italic>\n family genes,\n miR-10<\/jats:italic>\n ,\n miR-196a<\/jats:italic>\n ,\n miR-1<\/jats:italic>\n ,\n miR-193b<\/jats:italic>\n and\n miR-379<\/jats:italic>\n ) in AML. Subsequently, we further validated aberrant\n HOXB3<\/jats:italic>\n hypomethylation and its epigenetic regulatory role in AML.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n HOXB3<\/jats:italic>\n hypomethylation, which is associated with\n HOXB3<\/jats:italic>\n overexpression, is a frequent event in AML. AML with\n HOXB3<\/jats:italic>\n hypomethylation usually has unique genetic patterns such as a normal karyotype, cytogenetic\/molecular-intermediate risk, and mutations in\n FLT3<\/jats:italic>\n -ITD,\n NPM1<\/jats:italic>\n and\n DNMT3A<\/jats:italic>\n . Despite these associations,\n HOXB3<\/jats:italic>\n hypomethylation may serve as an independent prognostic biomarker for AML.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1709417","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T08:10:05Z","timestamp":1768205405000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification and validation of HOXB3 hypomethylation as a novel prognostically epigenetic biomarker in acute myeloid 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