IGH rod-like tracer: An AlphaFold2 structural similarity extraction-based predictive biomarker for minimal residual disease monitoring in children with precursor B-cell acute lymphoblastic leukemia

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, quantitative polymerase chain reaction (qPCR), or next-generation sequencing (NGS). This study aimed to identify immunoglobulin heavy-chain genes (IGH) rod-like tracer as an effective biomarker for dynamic minimal residual disease (MRD) monitoring in children with pre-B-ALL. 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 complementarity determining region 3 (CDR3) sequences (proportion > 5%) were identified, 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 children with pre-B-ALL during treatment. IGH rod-like tracer from quantitative immune repertoire sequencing may serve as a new class of biomarker with significant predictive values for the dynamic monitoring of MRD in children with pre-B-ALL.