biostudies-literatureUnknown16Chang LIn pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ B-ALL), the clinical value of highly sensitive minimal residual disease (MRD) detection by immunoglobulin next-generation sequencing (Ig-NGS), and its role for tracking clonal evolution, remains inadequately characterized. In this study, we evaluated MRD in a cohort of pediatric Ph+ B-ALL patients using Ig-NGS in parallel with conventional methods, including flow cytometry (FCM) and BCR-ABL reverse transcription polymerase chain reaction (RT-PCR). Malignant clonal burden at diagnosis, MRD kinetics, and immunoglobulin heavy chain (IGH) clonal evolution were analyzed for their prognostic relevance. We observed that a lower percentage of malignant clonal cells detected by Ig-NGS at diagnosis was associated with improved relapse-free survival (RFS) (p < 0.01). Ig-NGS-derived pre-treatment malignant clone burden showed stronger association with relapse risk compared with FCM or RT-PCR. Furthermore, Ig-NGS MRD negativity at the end of induction (EOI) was associated with superior two-yeas RFS (p = 0.01), and Ig-NGS detected molecular relapse earlier than FCM or RT-PCR in some patients. Specific IGHV and IGHJ gene usage patterns and the extent of V-replacement clonal evolution at diagnosis were also correlated with prognosis. In summary, these findings suggested that Ig-NGS based MRD assessment may provide enhanced prognostic stratification and enable dynamic monitoring of clonal evolution in pediatric Ph+ B-ALL. Its integration into routine clinical practice may enhance early relapse prediction and support more precise risk-adapted therapeutic decisions.Frontiers in immunology1677013https://www.ebi.ac.uk/biostudies/studies/S-EPMC12907345biostudies-literatureImmunoglobulin NGS enhance residual disease detection and prognosis in pediatric Ph+ acute lymphoblastic leukemia.PMC12907345Wu JChang LHu TZhao BGu YGuo YLu ZDong LZhang LLiu XZou YYang WRuan MLu SJia YChen YZhu XChen XWang XChang JDuan YfalseImmunoglobulin NGS enhance residual disease detection and prognosis in pediatric Ph+ acute lymphoblastic leukemia.In pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ B-ALL), the clinical value of highly sensitive minimal residual disease (MRD) detection by immunoglobulin next-generation sequencing (Ig-NGS), and its role for tracking clonal evolution, remains inadequately characterized. In this study, we evaluated MRD in a cohort of pediatric Ph+ B-ALL patients using Ig-NGS in parallel with conventional methods, including flow cytometry (FCM) and BCR-ABL reverse transcription polymerase chain reaction (RT-PCR). Malignant clonal burden at diagnosis, MRD kinetics, and immunoglobulin heavy chain (IGH) clonal evolution were analyzed for their prognostic relevance. We observed that a lower percentage of malignant clonal cells detected by Ig-NGS at diagnosis was associated with improved relapse-free survival (RFS) (p < 0.01). Ig-NGS-derived pre-treatment malignant clone burden showed stronger association with relapse risk compared with FCM or RT-PCR. Furthermore, Ig-NGS MRD negativity at the end of induction (EOI) was associated with superior two-yeas RFS (p = 0.01), and Ig-NGS detected molecular relapse earlier than FCM or RT-PCR in some patients. Specific IGHV and IGHJ gene usage patterns and the extent of V-replacement clonal evolution at diagnosis were also correlated with prognosis. In summary, these findings suggested that Ig-NGS based MRD assessment may provide enhanced prognostic stratification and enable dynamic monitoring of clonal evolution in pediatric Ph+ B-ALL. Its integration into routine clinical practice may enhance early relapse prediction and support more precise risk-adapted therapeutic decisions.2025-01-01T00:00:00Z20252026-07-16T05:17:06.697Z2026-07-09T13:10:12.867ZS-EPMC129073454170453610.3389/fimmu.2025.1677013