Gong Xiaowen, Hu Tianyuan, Shen Qiujin, Zhang Luyang, Zhang Wei, Liu Xueou, Zong Suyu, Li Xiaoyun, Wang Tiantian, Yan Wen, Hu Yu, Chen Xiaoli, Zheng Jiarui, Zhang Aoli, Wang Junxia, Feng Yahui, Li Chengwen, Ma Jiao, Gao Xin, Song Zhen, Zhang Yingchi, Gale Robert Peter, Zhu Xiaofan, Chen Junren
State 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 China.
Tianjin Institutes of Health Science Tianjin China.
EJHaem. 2024 Mar 15;5(2):333-345. doi: 10.1002/jha2.872. eCollection 2024 Apr.
:: 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 ::-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 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]; = 0.03). In an independent validation cohort of low-risk ::-positive B-cell ALL ( = 68) high expression at diagnosis had an HR = 4.78 [1.07, 21.36] ( = 0.04) for early relapse. In another validation cohort including 78 children with low-risk ::-negative B-cell ALL, high expression at diagnosis had an HR = 3.93 [1.31, 11.79] ( = 0.01). Our results suggest high expression at diagnosis in low-risk B-cell ALL in children might be associated with high risk for early relapse.
::是儿童急性淋巴细胞白血病（ALL）中最常见的融合基因，与良好预后相关，尤其是在低风险儿童中。然而，多达10%的儿童在3年内复发，且这种早期复发的生存率很低。识别有早期复发风险的儿童是一项重要挑战。我们分析了87例低风险::阳性B细胞ALL且有可用保存骨髓样本的儿童的数据（发现队列）。我们对一组559个基因中的体细胞点突变以及全基因组转录组和单核苷酸变体进行了分析。我们发现诊断时高表达（>第85百分位数）是早期复发最重要的独立预后因素（风险比[HR]=5.07[1.76,14.62]；=0.03）。在一个低风险::阳性B细胞ALL的独立验证队列（=68）中，诊断时高表达的早期复发HR=4.78[1.07,21.36]（=0.04）。在另一个包括78例低风险::阴性B细胞ALL儿童的验证队列中，诊断时高表达的早期复发HR=3.93[1.31,11.79]（=0.01）。我们的结果表明，儿童低风险B细胞ALL诊断时的高表达可能与早期复发的高风险相关。
