Immunogenetic Analysis of CTLA4 Polymorphisms, Serum Levels, and Hepatitis B Virus Coinfection in Iraqi Patients with Chronic Myeloid Leukemia

Document Type : New and original researches in the field of Microbiology.

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Department of Biology, College of Science, University of Babylon, Iraq

Abstract

Background: Chronic myeloid leukemia (CML) is driven by the BCR-ABL1 oncogene and characterized by dysregulated myeloid cell proliferation. Cytotoxic T-lymphocyte antigen-4 (CTLA4), an immune checkpoint protein, modulates T cell activity and may influence cancer progression. Tyrosine kinase inhibitors (TKIs) are effective in treating CML. Objectives: This study aimed to assess CTLA4 gene polymorphisms, serum CTLA4 levels, and HBV infection as potential risk factors in patients with chronic myeloid leukemia (CML). Methodology: A case-control study included 220 participants: 120 CML patients (20 newly diagnosed and 100 receiving treatment) and 100 age/sex-matched healthy controls. DNA was extracted from the blood samples, and CTLA4 polymorphisms (rs231775) were analyzed by PCR and Sanger sequencing. Serum CTLA4 levels were measured using ELISA. HBV DNA was detected by PCR. Statistical analyses included the chi-square test, Hardy-Weinberg equilibrium, and logistic regression. Results: CTLA4 genotype distributions differed significantly between the groups: CML patients exhibited 20% AA, 30% AT, and 50% TT, whereas controls showed 60% AA, 0% AT, and 40% TT. The AT genotype was exclusive to all patients (p=0.06, OR=0.05). Serum CTLA4 levels were higher in patients (32.47 ± 14.2 pg/mL) than controls (23.83 ± 9.03 pg/mL), though statistically significant (p=0.0387). HBV DNA was not detected in any sample. Biochemical parameters (urea, ALT, AST, and LDH) showed no significant differences, except for creatinine (p=0.01). Conclusion: CTLA4 polymorphisms, particularly the AT genotype, may confer a protective effect against CML development in Iraqi patients Elevated serum CTLA4 levels suggest immune dysregulation in CML; however, no association with HBV infection was observed. These findings do not support routine HBV screening in this cohort.

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