Department of Hematology, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Precision Medical Center, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
J Cell Mol Med. 2024 Oct;28(19):e70126. doi: 10.1111/jcmm.70126.
B-cell acute lymphoblastic leukaemia (B-ALL) is the most prevalent hematologic malignancy in children and a leading cause of mortality. Managing B-ALL remains challenging due to its heterogeneity and relapse risk. This study aimed to delineate the molecular features of paediatric B-ALL and explore the clinical utility of circulating tumour DNA (ctDNA). We analysed 146 patients with paediatric B-ALL who received systemic chemotherapy. The mutational landscape was profiled in bone marrow (BM) and plasma samples using next-generation sequencing. Minimal residual disease (MRD) testing on day 19 of induction therapy evaluated treatment efficacy. RNA sequencing identified gene fusions in 61% of patients, including 37 novel fusions. Specifically, the KMT2A-TRIM29 novel fusion was validated in a boy who responded well to initial therapy but relapsed after 1 year. Elevated mutation counts and maximum variant allele frequency in baseline BM were associated with significantly poorer chemotherapy response (p = 0.0012 and 0.028, respectively). MRD-negative patients exhibited upregulation of immune-related pathways (p < 0.01) and increased CD8 T cell infiltration (p = 0.047). Baseline plasma ctDNA exhibited high mutational concordance with the paired BM samples and was significantly associated with chemotherapy efficacy. These findings suggest that ctDNA and BM profiling offer promising prognostic insights for paediatric B-ALL management.
B 细胞急性淋巴细胞白血病（B-ALL）是儿童中最常见的血液系统恶性肿瘤，也是导致死亡的主要原因之一。由于其异质性和复发风险，B-ALL 的治疗仍然具有挑战性。本研究旨在描绘儿科 B-ALL 的分子特征，并探索循环肿瘤 DNA（ctDNA）的临床应用。我们分析了 146 名接受系统化疗的儿童 B-ALL 患者。采用下一代测序技术对骨髓（BM）和血浆样本进行突变景观分析。在诱导治疗第 19 天进行微小残留病（MRD）检测，评估治疗效果。RNA 测序在 61%的患者中鉴定出基因融合，包括 37 种新融合。具体来说，KMT2A-TRIM29 新型融合在一名男孩中得到验证，该男孩对初始治疗反应良好，但在 1 年后复发。基线 BM 中升高的突变计数和最大变异等位基因频率与化疗反应明显较差相关（p=0.0012 和 0.028，分别）。MRD 阴性患者表现出免疫相关途径的上调（p<0.01）和 CD8 T 细胞浸润增加（p=0.047）。基线血浆 ctDNA 与配对 BM 样本具有高度突变一致性，并与化疗疗效显著相关。这些发现表明，ctDNA 和 BM 分析为儿科 B-ALL 管理提供了有前途的预后见解。
