儿童 B 细胞急性淋巴细胞白血病 (B-ALL) 是一种高度异质性的疾病。根据大规模RNA测序（RNA-seq）数据，B-ALL患者可分为10多个亚组。然而，许多与耐药机制相关的基因组缺陷尚未被发现。作为分子诊断风险分类的个体临床工具，RNA-seq 和基于基因表达模式的治疗可能是未来潜在的策略。在这项研究中，我们回顾性分析了 45 名分子诊断分类与化疗反应不一致的儿童的 RNA-seq 基因表达谱。分析转录组与化疗反应之间的关系。对不具有已知高危相关融合基因或基因突变的纳入患者进行融合基因鉴定。在高危人群中最常检测到的融合基因对是 DHRSX 重复，这是一个新发现。发病时涉及 ABL1、LMNB2、NFATC1、PAX5 和 TTYH3 的融合在高危组中更常见，而涉及 LFNG、TTYH3 和 NFATC1 的融合在复发组中更常见。从涉及的途径来看，潜在的耐药机制与DNA甲基化、自噬和蛋白质代谢有关。总体而言，RNA-seq 诊断系统的实施将识别与化疗反应相关的激活标记物，并指导未来的治疗调整。© 2024。作者。

Pediatric B-cell acute lymphoblastic leukemia (B-ALL) is a highly heterogeneous disease. According to large-scale RNA sequencing (RNA-seq) data, B-ALL patients can be divided into more than 10 subgroups. However, many genomic defects associated with resistance mechanisms have not yet been identified. As an individual clinical tool for molecular diagnostic risk classification, RNA-seq and gene expression pattern-based therapy could be potential upcoming strategies. In this study, we retrospectively analyzed the RNA-seq gene expression profiles of 45 children whose molecular diagnostic classifications were inconsistent with the response to chemotherapy. The relationship between the transcriptome and chemotherapy response was analyzed. Fusion gene identification was conducted for the included patients who did not have known high-risk associated fusion genes or gene mutations. The most frequently detected fusion gene pair in the high-risk group was the DHRSX duplication, which is a novel finding. Fusions involving ABL1, LMNB2, NFATC1, PAX5, and TTYH3 at onset were more frequently detected in the high-risk group, while fusions involving LFNG, TTYH3, and NFATC1 were frequently detected in the relapse group. According to the pathways involved, the underlying drug resistance mechanism is related to DNA methylation, autophagy, and protein metabolism. Overall, the implementation of an RNA-seq diagnostic system will identify activated markers associated with chemotherapy response, and guide future treatment adjustments.© 2024. The Author(s).