{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T02:11:16Z","timestamp":1783476676202,"version":"3.55.0"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T00:00:00Z","timestamp":1753228800000},"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":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Alterations in multiple lipid metabolism pathways are associated with cancer progression. However, the relationship between lipid metabolism and central nervous system (CNS) relapse in acute myeloid leukemia (AML) remains unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted a retrospective analysis of 806 AML cases to evaluate the association between serum lipid levels and the risk of CNS relapse. Additionally, RNA-sequencing data from 895 AML patients were obtained from the TARGET database to identify hub lipid metabolism-related genes (LMRGs) associated with CNS relapse. <jats:italic>In vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic> experiments were performed to validate the bioinformatics findings.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Patients with CNS relapse exhibited significantly elevated levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) compared to the non-CNS relapse group. Hypercholesterolemia was identified as a risk factor for CNS relapse. RNA sequencing of AML patients with or without CNS relapse revealed 1,368 differentially expressed genes (DEGs). Functional enrichment analysis of the DEGs indicated a connection between lipid metabolism and CNS relapse. Through integrating these DEGs, LMRGs, and whole-genome correlation network analysis (WGCNA), carboxysterase 1 (CES1) was identified as a hub LMRG. High CES1 expression was a risk factor for CNS relapse and shorter overall survival. Moreover, CES1 influenced the proportion of nine types of tumor-infiltrating immune cells (TICs), particularly M2 macrophages, as supported by functional studies involving CES1 knockdown and overexpression in AML cells and AML xenograft tumor models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Hypercholesterolemia and CES1 can promote CNS relapse in AML patients, particularly through CES1\u2019s potential role in modulating immune infiltration within the TME.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1575472","type":"journal-article","created":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T05:35:19Z","timestamp":1753248919000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Hypercholesterolemia and the role of lipid metabolism gene CES1 in immune infiltration promote central nervous system relapse in acute myeloid 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