{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T16:32:42Z","timestamp":1767889962043,"version":"3.49.0"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T00:00:00Z","timestamp":1698710400000},"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>Introduction<\/jats:title><jats:p>Acute myeloid leukemia (AML) is a type of blood cancer that is identified by the unrestricted growth of immature myeloid cells within the bone marrow. Despite therapeutic advances, AML prognosis remains highly variable, and there is a lack of biomarkers for customizing treatment. RNA N6-methyladenosine (m<jats:sup>6<\/jats:sup>A) modification is a reversible and dynamic process that plays a critical role in cancer progression and drug resistance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To investigate the m<jats:sup>6<\/jats:sup>A modification patterns in AML and their potential clinical significance, we used the AUCell method to describe the m<jats:sup>6<\/jats:sup>A modification activity of cells in AML patients based on 23 m<jats:sup>6<\/jats:sup>A modification enzymes and further integrated with bulk RNA-seq data.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that m<jats:sup>6<\/jats:sup>A modification was more effective in leukemic cells than in immune cells and induced significant changes in gene expression in leukemic cells rather than immune cells. Furthermore, network analysis revealed a correlation between transcription factor activation and the m<jats:sup>6<\/jats:sup>A modification status in leukemia cells, while active m<jats:sup>6<\/jats:sup>A-modified immune cells exhibited a higher interaction density in their gene regulatory networks. Hierarchical clustering based on m<jats:sup>6<\/jats:sup>A-related genes identified three distinct AML subtypes. The immune dysregulation subtype, characterized by <jats:italic>RUNX1<\/jats:italic> mutation and <jats:italic>KMT2A<\/jats:italic> copy number variation, was associated with a worse prognosis and exhibited a specific gene expression pattern with high expression level of <jats:italic>IGF2BP3<\/jats:italic> and <jats:italic>FMR1<\/jats:italic>, and low expression level of <jats:italic>ELAVL1<\/jats:italic> and <jats:italic>YTHDF2<\/jats:italic>. Notably, patients with the immune dysregulation subtype were sensitive to immunotherapy and chemotherapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Collectively, our findings suggest that m<jats:sup>6<\/jats:sup>A modification could be a potential therapeutic target for AML, and the identified subtypes could guide personalized therapy.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1281687","type":"journal-article","created":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T11:13:15Z","timestamp":1698750795000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Integrated analysis of single-cell RNA-seq and bulk RNA-seq reveals RNA N6-methyladenosine modification associated with prognosis and drug resistance in acute myeloid 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