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. 2025 Mar;104(3):1821-1832.
doi: 10.1007/s00277-024-06102-2. Epub 2024 Nov 26.

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

Nesma E Abdelfattah  1 , Ghada M Elsayed  2 , Amira H Soliman  2 , Emad N Ebeid  3 , Mona S El Ashry  2
Affiliations

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

Nesma E Abdelfattah et al. Ann Hematol. 2025 Mar.

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.

Keywords: PAX5; RUNX1; ALL; BCP-ALL; FISH; MLPA.

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Conflict of interest statement

Declarations. Ethics approval and Informed consent to participate: was obtained from parent(s) or guardians of all pediatric individual participants included in the study. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the National Cancer Institute (NCI) Institutional Review Board (IRB) (number: 201920044.3/21.6.2020). Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
A: Frequency of copy number alteration of the studied genes by MLPA among the whole group of patients demonstrating that the most detected gene with CNAs was PAX5 gene. B: The frequency of deletions and duplications in the studied genes showing that CDKN2A/2B is the most deleted gene in our study while the most duplicated one was PAR1 complex (Xp22.33 / Yp11.32 region) C: Association of copy number alterations in the studied genes by MLPA with the ETV6::RUNX1 translocation showing that this translocation is significantly associated with CNAs in ETV6 gene. * All other: cases with normal copy number and cases with ambiguous copy number
Fig. 2
Fig. 2
A: Association between CNAs of PAX5 gene and OS, Patients with CNAs in PAX5 gene (exon 6) had a significantly lower OS (50% versus 85.7%, P = 0.012) versus normal copy number respectively B: association between PAX5 CNAs and EFS. Patients with CNAs in PAX5 (exon 6) had a significantly lower EFS than in those without (62.5% versus 88.6%, P = 0.025)
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