The IKAROS Transcription Factor Gene IKZF1 as a Critical Regulator in the Pathogenesis of Childhood Acute Lymphoblastic Leukemia: Insights from a Bangladeshi Population

The IKZF1 transcription factor gene plays a pivotal role in the commitment of multipotent progenitors to common lymphoid progenitors during lymphopoiesis. Genome-wide association studies (GWASs) have revealed an intriguing link between childhood acute lymphoblastic leukemia (ALL) and IKZF1 polymorphisms. This study investigated whether two specific IKZF1 variants, rs10272724 (T > C) and rs4132601 (T > G), are potential risk factors for childhood ALL among Bangladeshi children. In this study, we found that ALL occurs with a significantly greater frequency in male children than in female children, shedding light on potential sex-specific susceptibility patterns. Subsequent association analyses utilizing codominant, dominant, and recessive inheritance models demonstrated that rs10272724 is associated with a 2.36-fold increased risk of ALL development according to the codominant model, a 3.6-fold increased risk according to the dominant model, and a 1.84-fold increased risk according to the recessive model. Similarly, rs4132601 exhibited a substantial risk association, with a 3.58-fold increase in risk in the codominant model, a 3.85-fold increase in risk in the dominant model, and a 1.75-fold increase in risk in the recessive model. Furthermore, the analysis of haplotype frequencies revealed that the predominant haplotype, CG, is associated with a 1.3-fold greater risk for ALL development. Notably, we observed significant linkage disequilibrium patterns and constancy in genotypic frequencies, further strengthening the association of IKZF1 polymorphisms with ALL susceptibility. In conclusion, our study provides compelling evidence that two single-nucleotide polymorphisms (SNPs) located within the 3′ UTR of the IKZF1 gene are strongly associated with the development of childhood ALL in the Bangladeshi population.