Zhuo Zhongling, Wang Qingchen, Li Chang, Zhang Lili, Zhang Lanxin, You Ran, Gong Yan, Hua Ying, Miao Linzi, Bai Jiefei, Zhang Chunli, Feng Ru, Chen Meng, Su Fei, Qu Chenxue, Xiao Fei
Clinical Biobank, Beijing Hospital, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China.
The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Beijing Hospital, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China.
iScience. 2023 Jun 12;26(7):107107. doi: 10.1016/j.isci.2023.107107. eCollection 2023 Jul 21.
Sequence variation resulting from the evolution of IGH clones and immunophenotypic drift makes it difficult to track abnormal B cells in children with precursor B cell acute lymphoblastic leukemia (pre-B-ALL) by flow cytometry, qPCR, or next-generation sequencing (NGS). The V-(D)-J regions of immunoglobulin and T cell receptor of 47 pre-B-ALL samples were sequenced using the Illumina NovaSeq platform. The IGH rod-like tracer consensus sequence was extracted based on its rod-like alpha-helices structural similarity predicted by AlphaFold2. Additional data from published 203 pre-B-ALL samples were applied for validation. NGS-IGH (+) patients with pre-B-ALL had a poor prognosis. Consistent CDR3-coded protein structures in NGS-IGH (+) samples could be extracted as a potential follow-up marker for pre-B-ALL children during treatment. IGH rod-like tracer from quantitative immune repertoire sequencing may serve as a class of biomarker with significant predictive values for the dynamic monitoring of MRD in pre-B-ALL children.
IGH克隆的进化和免疫表型漂移导致的序列变异，使得通过流式细胞术、qPCR或下一代测序（NGS）追踪前体B细胞急性淋巴细胞白血病（pre - B - ALL）患儿中的异常B细胞变得困难。使用Illumina NovaSeq平台对47例pre - B - ALL样本的免疫球蛋白和T细胞受体的V-(D)-J区域进行测序。基于AlphaFold2预测的棒状α - 螺旋结构相似性，提取IGH棒状示踪剂共有序列。应用已发表的203例pre - B - ALL样本的其他数据进行验证。NGS - IGH(+)的pre - B - ALL患者预后较差。NGS - IGH(+)样本中一致的CDR3编码蛋白结构可作为pre - B - ALL患儿治疗期间潜在的随访标志物提取出来。定量免疫组库测序中的IGH棒状示踪剂可作为一类对pre - B - ALL患儿微小残留病动态监测具有显著预测价值的生物标志物。
