{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T05:24:55Z","timestamp":1762493095125,"version":"build-2065373602"},"reference-count":17,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T00:00:00Z","timestamp":1762473600000},"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. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Extrachromosomal circular DNA (eccDNA) plays critical roles in cancer, yet its landscape in acute myeloid leukemia (AML) remains unexplored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We used CIRCLE-seq and RNA-seq to characterize eccDNA in 12 AML patients and 4 healthy controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      AML cells showed significantly increased eccDNA counts and gene involvement versus healthy controls, with distinct size peaks at 202 and 368 bp. eccDNAs localized non-randomly to chromosomes 1, 2, and 10\u201319, enriching near transcription start sites and regulatory regions. Functional analysis revealed activation of oncogenic pathways (e.g., MAPK, ErbB signaling) in AML-associated eccDNA. Integrative analysis identified 570 genes upregulated at both the eccDNA and mRNA levels, including myeloid leukemia-related genes (e.g.,\n                      <jats:italic>FLT3<\/jats:italic>\n                      ,\n                      <jats:italic>RUNX1<\/jats:italic>\n                      , and\n                      <jats:italic>CD33<\/jats:italic>\n                      ) and oncogenes. Prognostic analysis showed that high expression of these genes correlated with poor outcomes in AML.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study unveils the eccDNA landscape in AML by direct CIRCLE-seq, linking its accumulation to transcriptional dysregulation and leukemogenesis, and highlights eccDNA as a potential biomarker and therapeutic target.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2025.1701989","type":"journal-article","created":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T05:21:40Z","timestamp":1762492900000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated CIRCLE-seq with RNA-seq to decipher the quantity, localization, and functional features of eccDNA in AML"],"prefix":"10.3389","volume":"15","author":[{"given":"Lijuan","family":"Gao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiongyu","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Changgen","family":"Ruan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhao","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suning","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-020-00960-9","article-title":"Current understanding of 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