Chromatin accessibility landscape of relapsed pediatric B-lineage acute lymphoblastic leukemia

Han Wang, Huiying Sun, Bilin Liang, Fang Zhang, Fan Yang, Bowen Cui, Lixia Ding, Xiang Wang, Ronghua Wang, Jiaoyang Cai, Yanjing Tang, Jianan Rao, Wenting Hu, Shuang Zhao, Wenyan Wu, Xiaoxiao Chen, Kefei Wu, Junchen Lai, Yangyang Xie, Benshang Li, Jingyan Tang, Shuhong Shen () and Yu Liu ()
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Han Wang: Shanghai Jiao Tong University
Huiying Sun: Shanghai Jiao Tong University
Bilin Liang: Shanghai Jiao Tong University
Fang Zhang: Shanghai Jiao Tong University
Fan Yang: Shanghai Jiao Tong University
Bowen Cui: Shanghai Jiao Tong University
Lixia Ding: Shanghai Jiao Tong University
Xiang Wang: Shanghai Jiao Tong University
Ronghua Wang: Shanghai Jiao Tong University
Jiaoyang Cai: Shanghai Jiao Tong University
Yanjing Tang: Shanghai Jiao Tong University
Jianan Rao: Shanghai Jiao Tong University
Wenting Hu: Shanghai Jiao Tong University
Shuang Zhao: Shanghai Jiao Tong University
Wenyan Wu: Shanghai Jiao Tong University
Xiaoxiao Chen: Shanghai Jiao Tong University
Kefei Wu: Shanghai Jiao Tong University
Junchen Lai: Shanghai Jiao Tong University
Yangyang Xie: Shanghai Jiao Tong University
Benshang Li: Shanghai Jiao Tong University
Jingyan Tang: Shanghai Jiao Tong University
Shuhong Shen: Shanghai Jiao Tong University
Yu Liu: Shanghai Jiao Tong University

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: Abstract For around half of the pediatric B-lineage acute lymphoblastic leukemia (B-ALL) patients, the molecular mechanism of relapse remains unclear. To fill this gap in knowledge, here we characterize the chromatin accessibility landscape in pediatric relapsed B-ALL. We observe rewired accessible chromatin regions (ACRs) associated with transcription dysregulation in leukemia cells as compared with normal B-cell progenitors. We show that over a quarter of the ACRs in B-ALL are in quiescent regions with high heterogeneity among B-ALLs. We identify subtype-specific and allele-imbalanced chromatin accessibility by integrating multi-omics data. By characterizing the differential ACRs between diagnosis and relapse in B-ALL, we identify alterations in chromatin accessibility during drug treatment. Further analysis of ACRs associated with relapse free survival leads to the identification of a subgroup of B-ALL which show early relapse. These data provide an advanced and integrative portrait of the importance of chromatin accessibility alterations in tumorigenesis and drug responses.

Date: 2023
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DOI: 10.1038/s41467-023-42565-z

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