Frontiers in oncology · 2025
Integrated CIRCLE-seq with RNA-seq to decipher the quantity, localization, and functional features of eccDNA in AML.
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Gao Lijuan, Lu Qiongyu, Li Hao, Ruan Changgen, Zeng Zhao, Chen Suning
Аннотация
BACKGROUND: Extrachromosomal circular DNA (eccDNA) plays critical roles in cancer, yet its landscape in acute myeloid leukemia (AML) remains unexplored.
METHODS: We used CIRCLE-seq and RNA-seq to characterize eccDNA in 12 AML patients and 4 healthy controls.
RESULTS: 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 10-19, 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., FLT3, RUNX1, and CD33) and oncogenes. Prognostic analysis showed that high expression of these genes correlated with poor outcomes in AML.
CONCLUSIONS: 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.
METHODS: We used CIRCLE-seq and RNA-seq to characterize eccDNA in 12 AML patients and 4 healthy controls.
RESULTS: 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 10-19, 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., FLT3, RUNX1, and CD33) and oncogenes. Prognostic analysis showed that high expression of these genes correlated with poor outcomes in AML.
CONCLUSIONS: 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.