Gene expression prognostic of early relapse risk in low‐risk B‐cell acute lymphoblastic leukaemia in children
Abstract ETV6::RUNX1 is the most common fusion gene in childhood acute lymphoblastic leukaemia (ALL) and is associated with favorable outcomes, especially in low‐risk children. However, as many as 10% of children relapse within 3 years, and such early relapses have poor survival. Identifying childre...
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| Language: | English |
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Wiley
2024-04-01
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| Series: | eJHaem |
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| Online Access: | https://doi.org/10.1002/jha2.872 |
| _version_ | 1797205200686022656 |
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| author | Xiaowen Gong Tianyuan Hu Qiujin Shen Luyang Zhang Wei Zhang Xueou Liu Suyu Zong Xiaoyun Li Tiantian Wang Wen Yan Yu Hu Xiaoli Chen Jiarui Zheng Aoli Zhang Junxia Wang Yahui Feng Chengwen Li Jiao Ma Xin Gao Zhen Song Yingchi Zhang Robert Peter Gale Xiaofan Zhu Junren Chen |
| author_facet | Xiaowen Gong Tianyuan Hu Qiujin Shen Luyang Zhang Wei Zhang Xueou Liu Suyu Zong Xiaoyun Li Tiantian Wang Wen Yan Yu Hu Xiaoli Chen Jiarui Zheng Aoli Zhang Junxia Wang Yahui Feng Chengwen Li Jiao Ma Xin Gao Zhen Song Yingchi Zhang Robert Peter Gale Xiaofan Zhu Junren Chen |
| author_sort | Xiaowen Gong |
| collection | DOAJ |
| description | Abstract ETV6::RUNX1 is the most common fusion gene in childhood acute lymphoblastic leukaemia (ALL) and is associated with favorable outcomes, especially in low‐risk children. However, as many as 10% of children relapse within 3 years, and such early relapses have poor survival. Identifying children at risk for early relapse is an important challenge. We interrogated data from 87 children with low‐risk ETV6::RUNX1‐positive B‐cell ALL and with available preserved bone marrow samples (discovery cohort). We profiled somatic point mutations in a panel of 559 genes and genome‐wide transcriptome and single‐nucleotide variants. We found high TIMD4 expression (> 85th‐percentile value) at diagnosis was the most important independent prognostic factor of early relapse (hazard ratio [HR] = 5.07 [1.76, 14.62]; p = 0.03). In an independent validation cohort of low‐risk ETV6::RUNX1‐positive B‐cell ALL (N = 68) high TIMD4 expression at diagnosis had an HR = 4.78 [1.07, 21.36] (p = 0.04) for early relapse. In another validation cohort including 78 children with low‐risk ETV6::RUNX1‐negative B‐cell ALL, high TIMD4 expression at diagnosis had an HR = 3.93 [1.31, 11.79] (p = 0.01). Our results suggest high TIMD4 expression at diagnosis in low‐risk B‐cell ALL in children might be associated with high risk for early relapse. |
| first_indexed | 2024-04-24T08:47:21Z |
| format | Article |
| id | doaj.art-2d19a6eea3e6454582900e1f537d85bf |
| institution | Directory Open Access Journal |
| issn | 2688-6146 |
| language | English |
| last_indexed | 2024-04-24T08:47:21Z |
| publishDate | 2024-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | eJHaem |
| spelling | doaj.art-2d19a6eea3e6454582900e1f537d85bf2024-04-16T13:16:29ZengWileyeJHaem2688-61462024-04-015233334510.1002/jha2.872Gene expression prognostic of early relapse risk in low‐risk B‐cell acute lymphoblastic leukaemia in childrenXiaowen Gong0Tianyuan Hu1Qiujin Shen2Luyang Zhang3Wei Zhang4Xueou Liu5Suyu Zong6Xiaoyun Li7Tiantian Wang8Wen Yan9Yu Hu10Xiaoli Chen11Jiarui Zheng12Aoli Zhang13Junxia Wang14Yahui Feng15Chengwen Li16Jiao Ma17Xin Gao18Zhen Song19Yingchi Zhang20Robert Peter Gale21Xiaofan Zhu22Junren Chen23State Key Laboratory of Experimental Hematology National Clinical Research Center for Blood Diseases Haihe Laboratory of Cell Ecosystem Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Tianjin ChinaState Key Laboratory of Experimental Hematology National Clinical Research Center for Blood Diseases Haihe Laboratory of Cell Ecosystem Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Tianjin ChinaState Key Laboratory of Experimental Hematology National Clinical Research Center for Blood Diseases Haihe Laboratory of Cell Ecosystem Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Tianjin ChinaState Key Laboratory of Experimental Hematology National Clinical Research Center for Blood Diseases Haihe Laboratory of Cell Ecosystem Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Tianjin ChinaState Key Laboratory of Experimental Hematology National Clinical Research Center for Blood Diseases Haihe Laboratory of Cell Ecosystem Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Tianjin ChinaState Key Laboratory of Experimental Hematology National Clinical Research Center for Blood Diseases Haihe Laboratory of Cell Ecosystem Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Tianjin ChinaState Key Laboratory of Experimental Hematology National Clinical Research Center for Blood Diseases Haihe Laboratory of Cell Ecosystem Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Tianjin ChinaState Key Laboratory of Experimental Hematology National Clinical Research Center for Blood Diseases Haihe Laboratory of Cell Ecosystem Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Tianjin ChinaState Key Laboratory of Experimental Hematology National Clinical Research Center for Blood Diseases Haihe Laboratory of Cell Ecosystem Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Tianjin ChinaState Key Laboratory of Experimental Hematology National Clinical Research Center for Blood Diseases Haihe Laboratory of Cell Ecosystem Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Tianjin ChinaState Key Laboratory of Experimental Hematology National Clinical Research Center for Blood Diseases Haihe Laboratory of Cell Ecosystem Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Tianjin ChinaState Key Laboratory of Experimental Hematology National Clinical Research Center for Blood Diseases Haihe Laboratory of Cell Ecosystem Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Tianjin ChinaState Key Laboratory of Experimental Hematology National Clinical Research Center for Blood Diseases Haihe Laboratory of Cell Ecosystem Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Tianjin ChinaState Key Laboratory of Experimental Hematology National Clinical Research Center for Blood Diseases Haihe Laboratory of Cell Ecosystem Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Tianjin ChinaState Key Laboratory of Experimental Hematology National Clinical Research Center for Blood Diseases Haihe Laboratory of Cell Ecosystem Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Tianjin ChinaState Key Laboratory of Experimental Hematology National Clinical Research Center for Blood Diseases Haihe Laboratory of Cell Ecosystem Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Tianjin ChinaState Key Laboratory of Experimental Hematology National Clinical Research Center for Blood Diseases Haihe Laboratory of Cell Ecosystem Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Tianjin ChinaState Key Laboratory of Experimental Hematology National Clinical Research Center for Blood Diseases Haihe Laboratory of Cell Ecosystem Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Tianjin ChinaState Key Laboratory of Experimental Hematology National Clinical Research Center for Blood Diseases Haihe Laboratory of Cell Ecosystem Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Tianjin ChinaState Key Laboratory of Experimental Hematology National Clinical Research Center for Blood Diseases Haihe Laboratory of Cell Ecosystem Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Tianjin ChinaState Key Laboratory of Experimental Hematology National Clinical Research Center for Blood Diseases Haihe Laboratory of Cell Ecosystem Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Tianjin ChinaDepartment of Immunology and Inflammation Centre for Haematology Imperial College of Science Technology and Medicine London UKState Key Laboratory of Experimental Hematology National Clinical Research Center for Blood Diseases Haihe Laboratory of Cell Ecosystem Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Tianjin ChinaState Key Laboratory of Experimental Hematology National Clinical Research Center for Blood Diseases Haihe Laboratory of Cell Ecosystem Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Tianjin ChinaAbstract ETV6::RUNX1 is the most common fusion gene in childhood acute lymphoblastic leukaemia (ALL) and is associated with favorable outcomes, especially in low‐risk children. However, as many as 10% of children relapse within 3 years, and such early relapses have poor survival. Identifying children at risk for early relapse is an important challenge. We interrogated data from 87 children with low‐risk ETV6::RUNX1‐positive B‐cell ALL and with available preserved bone marrow samples (discovery cohort). We profiled somatic point mutations in a panel of 559 genes and genome‐wide transcriptome and single‐nucleotide variants. We found high TIMD4 expression (> 85th‐percentile value) at diagnosis was the most important independent prognostic factor of early relapse (hazard ratio [HR] = 5.07 [1.76, 14.62]; p = 0.03). In an independent validation cohort of low‐risk ETV6::RUNX1‐positive B‐cell ALL (N = 68) high TIMD4 expression at diagnosis had an HR = 4.78 [1.07, 21.36] (p = 0.04) for early relapse. In another validation cohort including 78 children with low‐risk ETV6::RUNX1‐negative B‐cell ALL, high TIMD4 expression at diagnosis had an HR = 3.93 [1.31, 11.79] (p = 0.01). Our results suggest high TIMD4 expression at diagnosis in low‐risk B‐cell ALL in children might be associated with high risk for early relapse.https://doi.org/10.1002/jha2.872acute lymphoblastic leukaemiachildrenETV6::RUNX1leukaemia relapsemeasurable residual disease |
| spellingShingle | Xiaowen Gong Tianyuan Hu Qiujin Shen Luyang Zhang Wei Zhang Xueou Liu Suyu Zong Xiaoyun Li Tiantian Wang Wen Yan Yu Hu Xiaoli Chen Jiarui Zheng Aoli Zhang Junxia Wang Yahui Feng Chengwen Li Jiao Ma Xin Gao Zhen Song Yingchi Zhang Robert Peter Gale Xiaofan Zhu Junren Chen Gene expression prognostic of early relapse risk in low‐risk B‐cell acute lymphoblastic leukaemia in children eJHaem acute lymphoblastic leukaemia children ETV6::RUNX1 leukaemia relapse measurable residual disease |
| title | Gene expression prognostic of early relapse risk in low‐risk B‐cell acute lymphoblastic leukaemia in children |
| title_full | Gene expression prognostic of early relapse risk in low‐risk B‐cell acute lymphoblastic leukaemia in children |
| title_fullStr | Gene expression prognostic of early relapse risk in low‐risk B‐cell acute lymphoblastic leukaemia in children |
| title_full_unstemmed | Gene expression prognostic of early relapse risk in low‐risk B‐cell acute lymphoblastic leukaemia in children |
| title_short | Gene expression prognostic of early relapse risk in low‐risk B‐cell acute lymphoblastic leukaemia in children |
| title_sort | gene expression prognostic of early relapse risk in low risk b cell acute lymphoblastic leukaemia in children |
| topic | acute lymphoblastic leukaemia children ETV6::RUNX1 leukaemia relapse measurable residual disease |
| url | https://doi.org/10.1002/jha2.872 |
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