Integrated genomic analyses identify high-risk factors and actionable targets in T-cell acute lymphoblastic leukemia
Abstract. 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...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wolters Kluwer Health
2022-01-01
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| Series: | Blood Science |
| Online Access: | http://journals.lww.com/10.1097/BS9.0000000000000102 |
| _version_ | 1818314899699269632 |
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| author | Haichuan Zhu Bingjie Dong Yingchi Zhang Mei Wang Jianan Rao Bowen Cui Yu Liu Qian Jiang Weitao Wang Lu Yang Anqi Yu Zongru Li Chao Liu Leping Zhang Xiaojun Huang Xiaofan Zhu Hong Wu |
| author_facet | Haichuan Zhu Bingjie Dong Yingchi Zhang Mei Wang Jianan Rao Bowen Cui Yu Liu Qian Jiang Weitao Wang Lu Yang Anqi Yu Zongru Li Chao Liu Leping Zhang Xiaojun Huang Xiaofan Zhu Hong Wu |
| author_sort | Haichuan Zhu |
| collection | DOAJ |
| description | Abstract. 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 NOTCH1 mutations is significant lower in the Chinese T-ALL patients. Among 47 recurrently mutated genes in 7 functional categories, we identify RAS pathway and PTEN mutations as poor survival factors for non-TAL and TAL subtypes, respectively. Mutations in the PI3K pathway are mutually exclusive with mutations in the RAS and NOTCH1 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 RAS 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. |
| first_indexed | 2024-12-13T08:56:58Z |
| format | Article |
| id | doaj.art-e8d8a3fef7b3472b84cfbf94408d7df4 |
| institution | Directory Open Access Journal |
| issn | 2543-6368 |
| language | English |
| last_indexed | 2024-12-13T08:56:58Z |
| publishDate | 2022-01-01 |
| publisher | Wolters Kluwer Health |
| record_format | Article |
| series | Blood Science |
| spelling | doaj.art-e8d8a3fef7b3472b84cfbf94408d7df42022-12-21T23:53:16ZengWolters Kluwer HealthBlood Science2543-63682022-01-0141162810.1097/BS9.0000000000000102202201000-00004Integrated genomic analyses identify high-risk factors and actionable targets in T-cell acute lymphoblastic leukemiaHaichuan ZhuBingjie DongYingchi ZhangMei WangJianan RaoBowen CuiYu LiuQian JiangWeitao WangLu YangAnqi YuZongru LiChao LiuLeping ZhangXiaojun HuangXiaofan ZhuHong WuAbstract. 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 NOTCH1 mutations is significant lower in the Chinese T-ALL patients. Among 47 recurrently mutated genes in 7 functional categories, we identify RAS pathway and PTEN mutations as poor survival factors for non-TAL and TAL subtypes, respectively. Mutations in the PI3K pathway are mutually exclusive with mutations in the RAS and NOTCH1 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 RAS 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.http://journals.lww.com/10.1097/BS9.0000000000000102 |
| spellingShingle | Haichuan Zhu Bingjie Dong Yingchi Zhang Mei Wang Jianan Rao Bowen Cui Yu Liu Qian Jiang Weitao Wang Lu Yang Anqi Yu Zongru Li Chao Liu Leping Zhang Xiaojun Huang Xiaofan Zhu Hong Wu Integrated genomic analyses identify high-risk factors and actionable targets in T-cell acute lymphoblastic leukemia Blood Science |
| title | Integrated genomic analyses identify high-risk factors and actionable targets in T-cell acute lymphoblastic leukemia |
| title_full | Integrated genomic analyses identify high-risk factors and actionable targets in T-cell acute lymphoblastic leukemia |
| title_fullStr | Integrated genomic analyses identify high-risk factors and actionable targets in T-cell acute lymphoblastic leukemia |
| title_full_unstemmed | Integrated genomic analyses identify high-risk factors and actionable targets in T-cell acute lymphoblastic leukemia |
| title_short | Integrated genomic analyses identify high-risk factors and actionable targets in T-cell acute lymphoblastic leukemia |
| title_sort | integrated genomic analyses identify high risk factors and actionable targets in t cell acute lymphoblastic leukemia |
| url | http://journals.lww.com/10.1097/BS9.0000000000000102 |
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