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

• Published in: iScience Vol. 26; no. 7; p. 107107
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 21.07.2023; Elsevier
• Subjects: Cancer; Genomics; Molecular physiology; Molecular physiology; Genomics; Cancer
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2023.107107

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. [Display omitted] •The structure of IGH CDR3 have been predicted based on AlphaFold2 for the first time•IGH rod-like tracer has predictive values for the dynamic monitoring of MRD•IGH rod-like tracer may serve as a class of biomarker in pre-B-ALL children Molecular physiology; Cancer; Genomics