The landscape of extrachromosomal circular DNA (eccDNA) in the normal hematopoiesis and leukemia evolution

Abstract

Elevated extrachromosomal circular DNA (eccDNA) has been reported to accelerate tumor pathogenesis. Although the eccDNA profiles of other tumors have been established, the landscape of the eccDNA of acute myeloid leukemia (AML) has not been revealed. Our study first depicted the eccDNA profile of normal hematopoiesis and AML evolution by exploiting the ATAC-seq and RNA-seq data from nine healthy donors and 12 AML patients, which contained a total of 137 cell samples and 96 RNA-seq samples (including 16 blood cell types of the normal hematopoietic and AML hierarchies). We found the number of eccDNAs generally increased with the evolution of normal hematopoiesis and AML. The ecDNAs and ring chromosomes were found to reappear both in normal hematopoiesis and AML cells. Furthermore, we compared the eccDNAs of AML with normal cells. There were almost 300 AML-specific genes, including the known oncogenes NRAS, MCL1, EVI1, GATA2, WT1, and PAK1. And the ecDNA (chr11: 58668376-58826008) occurred in five out of 17 AML evolution-related cells, which was associated with the high expression of the GLYATL1 gene and the high expressed GLYATL1 was a poor prognostic factor. In conclusion, the eccDNA profiles of normal hematopoiesis and AML evolution were depicted and the recurrent eccDNAs we revealed might be utilized in the treatment of AML as biomarkers.

Extrachromosomal circular DNA in cancer drug resistance and its potential clinical implications

“…In acute myeloid leukemia (AML), the amount of eccDNA in cancer cells far exceeds that in normal cells. The average number of eccDNA gradually increased as primitive cells differentiated into terminal cells, and multiple recurrent and specific eccDNA were also identified in abnormal and normal cells ( 64 ). If the enrichment of eccDNA, especially the change of sequence, can predict the development of benign diseases into malignant cancers (such as hepatitis into liver cancer), eccDNA should be exhibited as a promising biomarker for cancer monitoring and prognosis.…”

EccBase: A high-quality database for exploration and characterization of extrachromosomal circular DNAs in cancer

“…The eccDNAs consisting of distinct chromosomal fragments were very few and therefore have not been incorporated into the current version. Finally, a total of 21 publications providing eccDNA information were retained [3] , [9] , [10] , [20] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] . Among them, 19, 2, 1 and 2 are related to hsa , mmu , gga and sce eccDNAs, respectively.…”

Categorizing Extrachromosomal Circular DNA as Biomarkers in Serum of Cancer

“…This suggests that the levels of eccDNA observed in plasma samples may be the result of multiple factors, including the process of cell-released DNA and subsequent experimental processing steps. During the progression of normal hematopoiesis and acute myeloid leukemia (AML), there is typically a rise in the abundance of eccDNA, suggesting a potential association between eccDNA and the pathophysiological processes of AML [91]. Lo's discovery of circulating fetal DNA in maternal plasma holds implications for non-invasive prenatal diagnosis [92], as further evidenced by Sin et al's observation of eccDNA in maternal plasma [93].…”