Transcriptome-wide subtyping of pediatric and adult T cell acute lymphoblastic leukemia in an international study of 707 cases
T cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy of T cell progenitors, known to be a heterogeneous disease in pediatric and adult patients. Here we attempted to better understand the disease at the molecular level based on the transcriptomic landscape of 707 T-A...
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my.um.eprints.428892023-08-29T07:32:19Z http://eprints.um.edu.my/42889/ Transcriptome-wide subtyping of pediatric and adult T cell acute lymphoblastic leukemia in an international study of 707 cases Dai, Yu-Ting Zhang, Fan Fang, Hai Li, Jian-Feng Lu, Gang Jiang, Lu Chen, Bing Mao, Dong-Dong Liu, Yuan-Fang Wang, Jin Peng, Li-Jun Feng, Chong Chen, Hai-Feng Mu, Jun-Xi Zhang, Qun-Ling Wang, Hao Ariffin, Hany Moy, Tan Ah Wang, Jing-Han Lou, Yin-Jun Chen, Su-Ning Wang, Qian Liu, Hong Shan, Zhe Matsumura, Itaru Miyazaki, Yasushi Yasuda, Takahiko Dou, Li-Ping Yan, Xiao-jing Yan, Jin-Song Yeoh, Allen Eng-Juh Wu, De-Pei Kiyoi, Hitoshi Hayakawa, Fumihiko Jin, Jie Wang, Sheng-Yue Sun, Xiao-Jian Mi, Jian-Qing Chen, Zhu Huang, Jin-Yan Chen, Sai-Juan Q Science (General) R Medicine (General) T cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy of T cell progenitors, known to be a heterogeneous disease in pediatric and adult patients. Here we attempted to better understand the disease at the molecular level based on the transcriptomic landscape of 707 T-ALL patients (510 pediatric, 190 adult patients, and 7 with unknown age; 599 from published cohorts and 108 newly investigated). Leveraging the information of gene expression enabled us to identify 10 subtypes (G1-G10), including the previously undescribed one characterized by GATA3 mutations, with GATA3(R276Q) capable of affecting lymphocyte development in zebrafish. Through associating with T cell differentiation stages, we found that high expression of LYL1/LMO2/SPI1/HOXA (G1-G6) might represent the early T cell progenitor, pro/precortical/cortical stage with a relatively high age of disease onset, and lymphoblasts with TLX3/TLX1 high expression (G7-G8) could be blocked at the cortical/post-cortical stage, while those with high expression of NKX2-1/TAL1/LMO1 (G9-G10) might correspond to cortical/post-cortical/mature stages of T cell development. Notably, adult patients harbored more cooperative mutations among epigenetic regulators, and genes involved in JAK-STAT and RAS signaling pathways, with 44% of patients aged 40 y or above in G1 bearing DNMT3A/IDH2 mutations usually seen in acute myeloid leukemia, suggesting the nature of mixed phenotype acute leukemia. Natl Acad Sciences India 2022-04 Article PeerReviewed Dai, Yu-Ting and Zhang, Fan and Fang, Hai and Li, Jian-Feng and Lu, Gang and Jiang, Lu and Chen, Bing and Mao, Dong-Dong and Liu, Yuan-Fang and Wang, Jin and Peng, Li-Jun and Feng, Chong and Chen, Hai-Feng and Mu, Jun-Xi and Zhang, Qun-Ling and Wang, Hao and Ariffin, Hany and Moy, Tan Ah and Wang, Jing-Han and Lou, Yin-Jun and Chen, Su-Ning and Wang, Qian and Liu, Hong and Shan, Zhe and Matsumura, Itaru and Miyazaki, Yasushi and Yasuda, Takahiko and Dou, Li-Ping and Yan, Xiao-jing and Yan, Jin-Song and Yeoh, Allen Eng-Juh and Wu, De-Pei and Kiyoi, Hitoshi and Hayakawa, Fumihiko and Jin, Jie and Wang, Sheng-Yue and Sun, Xiao-Jian and Mi, Jian-Qing and Chen, Zhu and Huang, Jin-Yan and Chen, Sai-Juan (2022) Transcriptome-wide subtyping of pediatric and adult T cell acute lymphoblastic leukemia in an international study of 707 cases. Proceedings of the National Academy of Sciences of the United States of America, 119 (15). ISSN 0027-8424, DOI https://doi.org/10.1073/pnas.2120787119 <https://doi.org/10.1073/pnas.2120787119>. 10.1073/pnas.2120787119 |
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Q Science (General) R Medicine (General) Dai, Yu-Ting Zhang, Fan Fang, Hai Li, Jian-Feng Lu, Gang Jiang, Lu Chen, Bing Mao, Dong-Dong Liu, Yuan-Fang Wang, Jin Peng, Li-Jun Feng, Chong Chen, Hai-Feng Mu, Jun-Xi Zhang, Qun-Ling Wang, Hao Ariffin, Hany Moy, Tan Ah Wang, Jing-Han Lou, Yin-Jun Chen, Su-Ning Wang, Qian Liu, Hong Shan, Zhe Matsumura, Itaru Miyazaki, Yasushi Yasuda, Takahiko Dou, Li-Ping Yan, Xiao-jing Yan, Jin-Song Yeoh, Allen Eng-Juh Wu, De-Pei Kiyoi, Hitoshi Hayakawa, Fumihiko Jin, Jie Wang, Sheng-Yue Sun, Xiao-Jian Mi, Jian-Qing Chen, Zhu Huang, Jin-Yan Chen, Sai-Juan Transcriptome-wide subtyping of pediatric and adult T cell acute lymphoblastic leukemia in an international study of 707 cases |
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T cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy of T cell progenitors, known to be a heterogeneous disease in pediatric and adult patients. Here we attempted to better understand the disease at the molecular level based on the transcriptomic landscape of 707 T-ALL patients (510 pediatric, 190 adult patients, and 7 with unknown age; 599 from published cohorts and 108 newly investigated). Leveraging the information of gene expression enabled us to identify 10 subtypes (G1-G10), including the previously undescribed one characterized by GATA3 mutations, with GATA3(R276Q) capable of affecting lymphocyte development in zebrafish. Through associating with T cell differentiation stages, we found that high expression of LYL1/LMO2/SPI1/HOXA (G1-G6) might represent the early T cell progenitor, pro/precortical/cortical stage with a relatively high age of disease onset, and lymphoblasts with TLX3/TLX1 high expression (G7-G8) could be blocked at the cortical/post-cortical stage, while those with high expression of NKX2-1/TAL1/LMO1 (G9-G10) might correspond to cortical/post-cortical/mature stages of T cell development. Notably, adult patients harbored more cooperative mutations among epigenetic regulators, and genes involved in JAK-STAT and RAS signaling pathways, with 44% of patients aged 40 y or above in G1 bearing DNMT3A/IDH2 mutations usually seen in acute myeloid leukemia, suggesting the nature of mixed phenotype acute leukemia. |
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Dai, Yu-Ting Zhang, Fan Fang, Hai Li, Jian-Feng Lu, Gang Jiang, Lu Chen, Bing Mao, Dong-Dong Liu, Yuan-Fang Wang, Jin Peng, Li-Jun Feng, Chong Chen, Hai-Feng Mu, Jun-Xi Zhang, Qun-Ling Wang, Hao Ariffin, Hany Moy, Tan Ah Wang, Jing-Han Lou, Yin-Jun Chen, Su-Ning Wang, Qian Liu, Hong Shan, Zhe Matsumura, Itaru Miyazaki, Yasushi Yasuda, Takahiko Dou, Li-Ping Yan, Xiao-jing Yan, Jin-Song Yeoh, Allen Eng-Juh Wu, De-Pei Kiyoi, Hitoshi Hayakawa, Fumihiko Jin, Jie Wang, Sheng-Yue Sun, Xiao-Jian Mi, Jian-Qing Chen, Zhu Huang, Jin-Yan Chen, Sai-Juan |
author_facet |
Dai, Yu-Ting Zhang, Fan Fang, Hai Li, Jian-Feng Lu, Gang Jiang, Lu Chen, Bing Mao, Dong-Dong Liu, Yuan-Fang Wang, Jin Peng, Li-Jun Feng, Chong Chen, Hai-Feng Mu, Jun-Xi Zhang, Qun-Ling Wang, Hao Ariffin, Hany Moy, Tan Ah Wang, Jing-Han Lou, Yin-Jun Chen, Su-Ning Wang, Qian Liu, Hong Shan, Zhe Matsumura, Itaru Miyazaki, Yasushi Yasuda, Takahiko Dou, Li-Ping Yan, Xiao-jing Yan, Jin-Song Yeoh, Allen Eng-Juh Wu, De-Pei Kiyoi, Hitoshi Hayakawa, Fumihiko Jin, Jie Wang, Sheng-Yue Sun, Xiao-Jian Mi, Jian-Qing Chen, Zhu Huang, Jin-Yan Chen, Sai-Juan |
author_sort |
Dai, Yu-Ting |
title |
Transcriptome-wide subtyping of pediatric and adult T cell acute lymphoblastic leukemia in an international study of 707 cases |
title_short |
Transcriptome-wide subtyping of pediatric and adult T cell acute lymphoblastic leukemia in an international study of 707 cases |
title_full |
Transcriptome-wide subtyping of pediatric and adult T cell acute lymphoblastic leukemia in an international study of 707 cases |
title_fullStr |
Transcriptome-wide subtyping of pediatric and adult T cell acute lymphoblastic leukemia in an international study of 707 cases |
title_full_unstemmed |
Transcriptome-wide subtyping of pediatric and adult T cell acute lymphoblastic leukemia in an international study of 707 cases |
title_sort |
transcriptome-wide subtyping of pediatric and adult t cell acute lymphoblastic leukemia in an international study of 707 cases |
publisher |
Natl Acad Sciences India |
publishDate |
2022 |
url |
http://eprints.um.edu.my/42889/ |
_version_ |
1776247437649772544 |
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13.18916 |