Integrated genomic analyses identify high-risk factors and actionable targets in T-cell acute lymphoblastic leukemia

• Published in: Blood science 2022-01, Vol.4 (1), p.16-28
• Main Authors: Zhu, Haichuan, Dong, Bingjie, Zhang, Yingchi, Wang, Mei, Rao, Jianan, Cui, Bowen, Liu, Yu, Jiang, Qian, Wang, Weitao, Yang, Lu, Yu, Anqi, Li, Zongru, Liu, Chao, Zhang, Leping, Huang, Xiaojun, Zhu, Xiaofan, Wu, Hong
• Format: Article
• Language: English
• ISSN: 2543-6368; 2543-6368
• DOI: 10.1097/BS9.0000000000000102

T cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy often associated with poor outcomes. To identify high-risk factors and potential actionable targets for T-ALL, we perform integrated genomic and transcriptomic analyses on samples from 165 Chinese pediatric and adult T-ALL patients, of whom 85% have outcome information. The genomic mutation landscape of this Chinese cohort is very similar to the Western cohort published previously, except that the rate of mutations is significant lower in the Chinese T-ALL patients. Among 47 recurrently mutated genes in 7 functional categories, we identify pathway and mutations as poor survival factors for non-TAL and TAL subtypes, respectively. Mutations in the pathway are mutually exclusive with mutations in the and pathways as well as transcription factors. Further analysis demonstrates that approximately 43% of the high-risk patients harbor at least one potential actionable alteration identified in this study, and T-ALLs with pathway mutations are hypersensitive to MEKi in vitro and in vivo. Thus, our integrated genomic analyses not only systematically identify high-risk factors but suggest that these high-risk factors are promising targets for T-ALL therapies.