Identification of rare and pathogenic TAL2 gene mutations in B-lineage acute lymphoblastic leukemia (B-ALL) using mutational screening and comprehensive bioinformatics analysis.

Background: Recent genomic research has identified several genetic factors contributing to B-cell acute lymphoblastic leukemia (B-ALL). However, the exact cause of the disease is still not fully understood. It is known that mutations in the TAL2 gene play important roles in the development of acute lymphoblastic leukemia. This study aimed to analyze the molecular and computational profile of the TAL2 mutations in a group of Iranian B-ALL patients for the first time.

Methods And Results: In this study, 188 patients were enrolled, and the TAL2 gene was sequenced to identify gene variations. The study included structural/functional analysis, homology modeling, molecular docking, and molecular dynamics (MD) simulations to assess the potential impact of the missense mutations on the protein's structure. Three nucleotide variations in the exon, three variations in the 3'UTR, and one deletion variant in the 3'UTR were detected in patients. Through in-silico analysis, it was found that the p. Asp35Glu missense mutation is located in the bHLH domain of the TAL2 protein. Also, the structural and functional analyses predicted that this mutation is a pathogenic or likely pathogenic variant in B-ALL patients. Moreover, a multiple nucleotide deletion (g.659_668del) was found in the 3'UTR in most patients. This deletion occurs at the site of poly-A tail attachment and appears to have significant implications.

Conclusions: These findings offer new insights into the impact of genetic variants in the TAL2 gene on the development of B-ALL and their potential role as tumor biomarkers for the B-ALL. Further research is needed to explore the relationship between specific TAL2 mutations and the clinical presentation of B-ALL.