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

Tiansheng Zeng; Wenhui Huang; Longzhen Cui; Pei Zhu; Qing Lin; Wenjuan Zhang; Junyi Li; Cong Deng; Zhihua Wu; Zeyong Huang; Zhiyong Zhang; Tingting Qian; Wei Xie; Min Xiao; Yingyu Chen; Lin Fu

doi:10.1038/s41420-022-01189-w

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

Cell Death Discov. 2022 Sep 28;8(1):400. doi: 10.1038/s41420-022-01189-w.

Authors

Tiansheng Zeng^#^{1

2

3}, Wenhui Huang^#^{1

2}, Longzhen Cui^#^{4

5}, Pei Zhu^{1

2}, Qing Lin^{1

2}, Wenjuan Zhang^{1

2}, Junyi Li^{1

2}, Cong Deng^{1

2

6}, Zhihua Wu^{1

2}, Zeyong Huang^{1

2}, Zhiyong Zhang^{1

2}, Tingting Qian^{1

2}, Wei Xie¹, Min Xiao^{1

2}, Yingyu Chen⁷, Lin Fu^{8

9}

Affiliations

¹ Department of Hematology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, P. R. China.
² Central Laboratory, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, P. R. China.
³ Translational Medicine Center, Guangzhou Key Laboratory for Research and Development of Nano-Biomedical Technology for Diagnosis and Therapy &Guangdong Provincial Education Department Key Laboratory of Nano-Immunoregulation Tumour Microenvironment, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, P. R. China.
⁴ Translational Medicine Center, Huaihe Hospital of Henan University, Kaifeng, Henan, P. R. China.
⁵ Department of Hematology, Huaihe Hospital of Henan University, Kaifeng, Hena, P. R. China.
⁶ Department of Clinical Laboratory, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, P. R. China.
⁷ Department of Hematology, Fujian Institute of Hematology, Fujian Medical University Union Hospital, Fuzhou, Fujian, P. R. China.
⁸ Department of Hematology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, P. R. China. fulin022@126.com.
⁹ Central Laboratory, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, P. R. China. fulin022@126.com.

^# Contributed equally.

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.

Abstract

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