Clinical profile, genomic insights, and novel variants in Pakistani pediatric B-ALL patients

Abstract

Objectives: To determine the genomic and molecular alterations in a sample set of Pakistani pediatric B- Acute Lymphoblastic leukemia (B-ALL) patients. Methodology: This descriptive analytical study was conducted at the University of Health Sciences, Lahore, Pakistan, from November 2021 to June 2022. Newly diagnosed treatment-naïve pediatric B-ALL patients were enrolled. Following DNA isolation, whole genome sequencing (WGS) was performed and genomic variants were analyzed using the Genome Analysis Tool Kit (GATK). Results: Of the 19 enrolled B-ALL patients, whole genome sequencing data of sufficient quality for variant analysis were available for 12 patients. Single nucleotide variations (SNVs) and INDELs were identified in all 12 of these patients, each carrying a variant in one of four genes: SLC6A4 (n=7, 58%), ZFHX3 (n=3, 25%), SLC26A9 (n=1, 8%), and BRCA2 (n=1, 8%). Conclusion: Immunophenotypic variations and genomic alterations including SNVs and indels were evident in the enrolled B-ALL patients. Extensive efforts are warranted to understand the impact of these genomic and molecular changes in B-ALL for better risk assessment and prediction of prognosis and disease management.