Integrated Copy Number and Mutation Profiling Identifies Novel Prognostic Markers of Poor Survival in B-ALL
Sooyoung Pee
Saint Johnsbury Academy Jeju, Jeju, South Korea
Publication date: November 20, 2025
Saint Johnsbury Academy Jeju, Jeju, South Korea
Publication date: November 20, 2025
DOI: http://doi.org/10.34614/JIYRC2025II49
ABSTRACT
B-cell acute lymphoblastic leukemia (B-ALL) is a lethal hematologic malignancy with poor survival in adults, highlighting the need for new prognostic biomarkers. We performed integrated genomic analyses to compare deceased and surviving B-ALL patients. Copy number variation analysis revealed recurrent deletions in the immunoglobulin heavy chain variable (IGHV) locus at 14q32.33, including IGHV3-65, IGHV3-66, IGHV3-48, IGHV1-45, and IGHV1-46. These deletions were significantly enriched in deceased patients (13–17%) compared to survivors (1–2%) and were mapped to immune signaling pathways such as CD22-mediated B-cell receptor regulation, classical complement activation, and Fc receptor signaling, suggesting impaired immune surveillance. Mutation profiling further identified enrichment of NT5C2, TP53, and JAK2 in deceased patients, consistent with therapy resistance, genomic instability, and aberrant cytokine signaling, along with novel candidates including ZAN, CSF1R, and GLIPR1. Gene network analysis revealed that NT5C2 and TP53 acted as central hubs in a co-expression–dominated module, linking both established and novel mutations. Together, these findings highlight IGHV deletions and recurrent mutations as complementary genomic features of poor prognosis in B-ALL, supporting their potential as integrated prognostic biomarkers.
B-cell acute lymphoblastic leukemia (B-ALL) is a lethal hematologic malignancy with poor survival in adults, highlighting the need for new prognostic biomarkers. We performed integrated genomic analyses to compare deceased and surviving B-ALL patients. Copy number variation analysis revealed recurrent deletions in the immunoglobulin heavy chain variable (IGHV) locus at 14q32.33, including IGHV3-65, IGHV3-66, IGHV3-48, IGHV1-45, and IGHV1-46. These deletions were significantly enriched in deceased patients (13–17%) compared to survivors (1–2%) and were mapped to immune signaling pathways such as CD22-mediated B-cell receptor regulation, classical complement activation, and Fc receptor signaling, suggesting impaired immune surveillance. Mutation profiling further identified enrichment of NT5C2, TP53, and JAK2 in deceased patients, consistent with therapy resistance, genomic instability, and aberrant cytokine signaling, along with novel candidates including ZAN, CSF1R, and GLIPR1. Gene network analysis revealed that NT5C2 and TP53 acted as central hubs in a co-expression–dominated module, linking both established and novel mutations. Together, these findings highlight IGHV deletions and recurrent mutations as complementary genomic features of poor prognosis in B-ALL, supporting their potential as integrated prognostic biomarkers.
