Copy number alterations in pediatric B-cell precursor acute lymphoblastic leukemia patients and their association with patients’ outcome

TL;DR

This study examines how genetic copy number changes in pediatric B-cell leukemia patients affect their survival and treatment response.

Contribution

The study identifies PAX5 and ETV6 copy number alterations as significant prognostic markers in pediatric BCP-ALL.

Findings

PAX5 copy number alterations are linked to worse overall and event-free survival.

ETV6 copy number increases correlate with higher minimal residual disease on day 15.

PAX5 CNA is associated with RUNX1 gene gain and translocation.

Abstract

Genetic abnormalities provide diagnostic and prognostic information for pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) patients. The aim of this study was to determine the effects of genetic CNAs and RUNX1 gene abnormalities on the outcome of pediatric BCP-ALL patients. This study included 78 de novo-BCP-ALL pediatric patients who presented to the Pediatric Oncology Department of the National Cancer Institute (NCI), Cairo University. We aimed to study the impact of copy number alteration (CNA) of 8 of the most altered genes in BCP-ALL patients, in addition to RUNX1 gene abnormalities, on patient survival and response to treatment. Multiplex ligation-dependent probe amplification (MLPA) was used to detect CNA, while RUNX1 gene alterations were detected by fluorescence in situ hybridization (FISH). CNA of the PAX5 gene was significantly associated with worse overall survival (OS) and event-free survival (EFS) (P = 0.012 and P = 0.025, respectively). An increase in the CNA of ETV6 was associated with an increase in minimal residual disease (MRD) on day 15 (P = 0.041). Although RUNX1 gene abnormalities were not a predictor of shorter OS or EFS, an interesting significant association was found between PAX5 CNA and RUNX1 gene gain and translocation (P = 0.017 and P = 0.041, respectively). PAX5 CNA is an adverse prognostic factor. ETV6 CNA is associated with high MRD on day 15.

The online version contains supplementary material available at 10.1007/s00277-024-06102-2.

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