IGH rod-like tracer: An AlphaFold2 structural similarity extraction-based predictive biomarker for MRD monitoring in pre-B-ALL

IGH 棒状示踪剂:基于 AlphaFold2 结构相似性提取的预测性生物标志物,用于 B 型急性淋巴细胞白血病前期的 MRD 监测

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作者:Zhongling Zhuo, Qingchen Wang, Chang Li, Lili Zhang, Lanxin Zhang, Ran You, Yan Gong, Ying Hua, Linzi Miao, Jiefei Bai, Chunli Zhang, Ru Feng, Meng Chen, Fei Su, Chenxue Qu, Fei Xiao

Abstract

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.

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