Therapy-Acquired Clonal Mutations in Thiopurine Drug-Response Genes Drive Majority of Early Relapses in Pediatric B-Cell Precursor Acute Lymphoblastic Leukemia

ABSTRACT: Methods: Forty pediatric (0–12 years) B-ALL DNA samples (20 paired Diagnosis-Relapse) and an additional six B-ALL DNA samples (without relapse at 3 years post treatment), as the non-relapse arm, were retrieved from the biobank for advanced genomic analysis. Deep sequencing (1050–5000X; mean 1600X) was performed using a custom NGS panel of 74 genes incorporating unique molecular barcodes. Results: A total 47 major clones (>25% VAF) and 188 minor clones were noted in 40 cases after bioinformatic data filtering. Of the forty-seven major clones, eight (17%) were diagnosis-specific, seventeen (36%) were relapse-specific and 11 (23%) were shared. In the control arm, no pathogenic major clone was noted in any of the six samples. The most common clonal evolution pattern observed was therapy-acquir

SUBMITTER: Thakur R 

PROVIDER: S-EPMC10001400 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature