J Pediatr Genet 2023; 12(04): 288-300
DOI: 10.1055/s-0041-1742246
Original Article

Genetic Profiling of Pediatric Patients with B-Cell Precursor Acute Lymphoblastic Leukemia

1   Department of Medical Biology, Faculty of Medicine, Niğde Ömer Halisdemir University, Niğde, Turkey
2   Department of Biostatistic, Faculty of Medicine, Biostatistics, Ankara University, Ankara, Turkey
3   Atatürk Vocational School of Health Services, Afyonkarahisar Health Sciences University, Afyonkarahisar, Turkey
4   LÖSANTE Children's and Adult Hospital, Ankara, Turkey
4   LÖSANTE Children's and Adult Hospital, Ankara, Turkey
4   LÖSANTE Children's and Adult Hospital, Ankara, Turkey
5   Department of Pediatrics, TOBB-ETU Hospital, Ankara, Turkey
6   Ankara University Biotechnology Institute, Ankara, Turkey
› Author Affiliations
Funding This work was supported by grants from the Scientific and Technological Research Council of Turkey (TUBITAK) (project no. 114S030) and Ankara University Scientific Research Projects Office (project no. 14L0415002).


B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is a heterogeneous leukemia subgroup. It has multiple sub-types that are likely to be classified by prognostic factors. Following a systematic literature review, this study analyzed the genes correlated with BCP-ALL prognosis (IKZF1, PAX5, EBF1, CREBBP, CRLF2, JAK2, ERG, CXCR4, ZAP70, VLA4, NF1, NR3C1, RB1, TSLP, ZNRF1, and FOXO3A), specifically their nucleotide variations and expression profiles in pediatric BCP-ALL samples. The study included 45 pediatric BCP-ALL patients with no cytogenetic anomaly and a control group of 10 children. The selected genes' hot-spot regions were sequenced using next-generation sequencing, while Polymorphism Phenotyping v2 and Supplemental Nutrition Assistance Program were used to identify pathogenic mutations. The expression analysis was performed using quantitative real-time polymerase chain reaction. The mutation analysis detected 328 variants (28 insertions, 47 indels, 74 nucleotide variants, 75 duplications, and 104 deletions). The most and least frequently mutated genes were IKZF1 and CREBBP, respectively. There were statistically significant differences between patients and controls for mutation distribution in eight genes (ERG, CRLF2, CREBBP, TSLP, JAK2, ZAP70, FOXO3A, and NR3C1). The expression analysis revealed that JAK and ERG were significantly overexpressed in patients compared with controls (respectively, p = 0.004 and p = 0.003). This study combined genes and pathways previously analyzed in pediatric BCP-ALL into one dataset for a comprehensive analysis from the same samples to unravel candidate prognostic biomarkers. Novel mutations were identified in all of the studied genes.

Supplementary Material

Publication History

Received: 06 August 2021

Accepted: 09 December 2021

Article published online:
10 February 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag KG
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