Distinct genomic landscape of Chinese pediatric acute myeloid leukemia impacts clinical risk classification

Ting Liu, Jianan Rao, Wenting Hu, Bowen Cui, Jiaoyang Cai, Yuhan Liu, Huiying Sun, Xiaoxiao Chen, Yanjing Tang, Jing Chen, Xiang Wang, Han Wang, Wubin Qian, Binchen Mao, Sheng Guo, Ronghua Wang, Yu Liu () and Shuhong Shen ()
Additional contact information
Ting Liu: Shanghai Jiao Tong University
Jianan Rao: Shanghai Jiao Tong University
Wenting Hu: Shanghai Jiao Tong University
Bowen Cui: Shanghai Jiao Tong University
Jiaoyang Cai: Shanghai Jiao Tong University
Yuhan Liu: Shanghai Jiao Tong University
Huiying Sun: Shanghai Jiao Tong University
Xiaoxiao Chen: Shanghai Jiao Tong University
Yanjing Tang: Shanghai Jiao Tong University
Jing Chen: Shanghai Jiao Tong University
Xiang Wang: Shanghai Jiao Tong University
Han Wang: Shanghai Jiao Tong University
Wubin Qian: Crown Bioscience Inc.
Binchen Mao: Crown Bioscience Inc.
Sheng Guo: Crown Bioscience Inc.
Ronghua Wang: Shanghai Jiao Tong University
Yu Liu: Shanghai Jiao Tong University
Shuhong Shen: Shanghai Jiao Tong University

Nature Communications, 2022, vol. 13, issue 1, 1-11

Abstract: Abstract Studies have revealed key genomic aberrations in pediatric acute myeloid leukemia (AML) based on Western populations. It is unknown to what extent the current genomic findings represent populations with different ethnic backgrounds. Here we present the genomic landscape of driver alterations of Chinese pediatric AML and discover previously undescribed genomic aberrations, including the XPO1-TNRC18 fusion. Comprehensively comparing between the Chinese and Western AML cohorts reveal a substantially distinct genomic alteration profile. For example, Chinese AML patients more commonly exhibit mutations in KIT and CSF3R, and less frequently mutated of genes in the RAS signaling pathway. These differences in mutation frequencies lead to the detection of previously uncharacterized co-occurring mutation pairs. Importantly, the distinct driver profile is clinical relevant. We propose a refined prognosis risk classification model which better reflected the adverse event risk for Chinese AML patients. These results emphasize the importance of genetic background in precision medicine.

Date: 2022
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DOI: 10.1038/s41467-022-29336-y

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