Integrated CIRCLE-seq with RNA-seq to decipher the quantity, localization, and functional features of eccDNA in AML

Area of Science:

• Genomics
• Cancer Biology
• Molecular Oncology

Background:

• Extrachromosomal circular DNA (eccDNA) is implicated in cancer development.
• The role and characteristics of eccDNA in acute myeloid leukemia (AML) are largely unknown.

Purpose of the Study:

• To comprehensively characterize the eccDNA landscape in AML.
• To investigate the association between eccDNA and gene expression in AML.
• To explore the potential of eccDNA as a biomarker and therapeutic target in AML.

Main Methods:

• Utilized CIRCLE-seq and RNA-seq for eccDNA and mRNA profiling.
• Analyzed eccDNA in 12 AML patients and 4 healthy controls.
• Performed integrative and prognostic analyses.

Main Results:

• AML patients exhibited significantly higher eccDNA counts and gene involvement compared to healthy controls.
• Identified distinct eccDNA size peaks (202 and 368 bp) and non-random chromosomal localization.
• Found activation of oncogenic pathways and identified 570 genes upregulated at both eccDNA and mRNA levels, including key myeloid leukemia genes (e.g., FLT3, RUNX1, CD33).
• High expression of these genes correlated with poor AML prognosis.

Conclusions:

• This study provides the first comprehensive view of the eccDNA landscape in AML.
• eccDNA accumulation is linked to transcriptional dysregulation and leukemogenesis.
• eccDNA represents a promising biomarker and therapeutic target for AML.