ABSTRACT. The PAX5 gene, which encodes the B-cell specific activator protein, is one of the most important factors in determination of B-cell development. This gene is the main target of somatic mutations in acute B lymphoblastic leukemia (B-ALL). For example, point mutations, deletions, as well as other gene rearrangements may lead to several forms of B-cell malignancy. In this study, we obtained 50 blood samples from patients diagnosed with ALL, and screened for PAX5 mutations using sequencing in exons 1, 2 and 3. We found a heterozygous germline variant, c.113G>A (p.Arg38His), which affects the paired domain of PAX5. It seems that this mutation is pathogenic, but is recessive. Our findings suggest that this mutation in a single allele of the PAX5 gene is not sufficient to cause disease, and it is possible that other alleles are also involved in the onset of B-ALL.

Background: Acute lymphoblastic leukemia (ALL) is a malignant disorder of lymphoid progenitor cells that affects both children and adults. B-lineage acute lymphoblastic leukemia (B-ALL) that derived from primary B cell precursors is a common subtype of ALL. PAX5 is a member of PAX gene family. This gene is located at 9p13.2, encoding the B-cell lineage specific activator protein (BSAP). BSAP is an essential regulator of B lymphocytes identity and function which plays an important role in part of B cell specific genes. Objectives: The aim of this study is to screen probable variants in flanking regions of introns 1 and 2 near the exons 1, 2 and 3 of PAX5 gene among BALL patients from Khuzestan province. Patients and Methods: In this descriptive study, blood samples were collected from 50 patients with clinical symptoms of BALL in Khuzestan province. In order to identify the probable variants in introns 1 and 2 near the exons 1, 2 and 3 of PAX5 gene, flanking regions of introns amplified by PCR and the products were sequenced for any probable change. Results: Two variants in nine patients were identified including IVS2-43T > C and IVS2 + 11T > G. IVS2-43T > C variant was found as a heterozygous form in one patient and IVS2 + 11T > G was found as a homozygous variant in 8 patients with BALL. Conclusions: The overall frequency of variants in intron 2 of PAX5 gene was 18%. IVS2 + 11T > G variant of PAX5 gene probably do not associated with BALL risk in the population.