Li Fu, Yang Xiaomei, Wang Xiuxiu, Mi Jiajia, Mou Xiao, Song Li, Zheng Libo
Department of Hematology and Oncology, Children's Hospital Affiliated to Shandong University and Jinan Children's Hospital, Jinan, Shandong, 250022, P.R. China.
Chigene (Beijing) Translational Medical Research Center Co., Ltd., Beijing, China.
Curr Genomics. 2025;26(2):144-159. doi: 10.2174/0113892029319425240813074610. Epub 2024 Aug 21.
B-ALL is a hematologic malignancy that recurs in approximately 10-20% of children and has a poor prognosis. New prognostic biomarkers are needed to improve individualized therapy and achieve better clinical outcomes.
In this study, high-throughput sequencing technology was used to detect the BCR and TCR repertoires in children with B-ALL.
We observed a gradual increase in the diversity of the BCR and TCR repertoires during the developmental stages (Pro-, Common-, Pre-B-ALL) of precursor B-ALL cells. Conversely, as minimal residual disease (MRD) levels on day 19 of induction therapy increased, the BCR/TCR repertoire diversity decreased. Furthermore, the BCR/TCR repertoire diversity was significantly greater in B-ALL patients at low risk and those harboring the ETV6/RUNX1 fusion than in patients with medium-risk disease and those harboring the ZNF384 fusion. Notably, the abundance of BCR/TCR clones varied significantly among patients with B-ALL and different clinical characteristics. Specifically, patients with Pre-B-ALL, low-risk disease, D19MRD levels <1%, and harboring the ETV6/RUNX1 fusion exhibited a predominance of BCR/TCR small clones. In our study, we noted an imbalanced occurrence of V and J gene utilization among patients with B-ALL; however, there seemed to be no discernible correlation with the clinical attributes.
BCR/TCR repertoires are expected to be potential prognostic biomarkers for patients with B-ALL.
B淋巴细胞白血病（B-ALL）是一种血液系统恶性肿瘤，约10%-20%的儿童会复发，预后较差。需要新的预后生物标志物来改善个体化治疗并取得更好的临床结果。
在本研究中，采用高通量测序技术检测B-ALL患儿的BCR和TCR库。
我们观察到在前体B-ALL细胞的发育阶段（原B-ALL、普通B-ALL、前B-ALL），BCR和TCR库的多样性逐渐增加。相反，随着诱导治疗第19天微小残留病（MRD）水平的升高，BCR/TCR库多样性降低。此外，低风险B-ALL患者以及携带ETV6/RUNX1融合基因的患者的BCR/TCR库多样性显著高于中风险疾病患者以及携带ZNF384融合基因的患者。值得注意的是，B-ALL患者中BCR/TCR克隆的丰度因不同临床特征而有显著差异。具体而言，前B-ALL、低风险疾病、诱导治疗第19天MRD水平<1%且携带ETV6/RUNX1融合基因的患者表现为BCR/TCR小克隆占优势。在我们的研究中，我们注意到B-ALL患者中V和J基因利用存在不均衡现象；然而，这似乎与临床特征没有明显相关性。
BCR/TCR库有望成为B-ALL患者潜在的预后生物标志物。
