TIM3 and CTLA4 immune checkpoint polymorphisms are associated with acute myeloid leukemia in Saudi Arabia

ABSTRACT

Background

Immune checkpoints are receptors on the surface of T cells that function crucially in suppressing the immune response, and they are implicated in autoimmunity and cancer diseases.

Aim

The present study aimed to investigate the relationship between functional single nucleotide polymorphisms (SNPs) of two immune checkpoint molecules, CTLA-4 and TIM-3, and acute myeloid leukemia (AML) in a Saudi population.

Methods

Two SNPs in CTLA-4 (rs231775, A > G) and TIM-3 (rs10515746, A > C) were genotyped in 229 subjects, including 98 patients and 131 healthy controls, from the Saudi population using TaqMan assay methods. Differential expression of these two genes was performed using in silico analysis.

Results

An association was found between polymorphisms in TIM-3 (OR: 6.01; 95% CI: 3.99–9.05, P < 0.0001) and the risk of AML. Inversely, the rs231775 SNP in the CTLA-4 gene was found to protect against AML in allelic, dominant, and additive models (P < 0.05). A significantly higher expression of TIM-3 in the blood of individuals with AML was observed.

Conclusion

This is the first study focusing on single nucleotide polymorphisms (SNPs) for CTLA-4 and TIM-3 in acute myeloid leukemia patients in a Saudi community and could be a potential new prognostic factor for this disease.

KEYWORDS:

• Hematological malignancy
• CTLA-4
• TIM-3‌
• Immune checkpoint molecules
• single nucleotide polymorphism
• acute myeloid leukemia
• Saudi Arabia

Acknowledegments

The authors extend their appreciation to the Researchers Supporting Project number (RSP2024R75), King Saudi University, Riyadh, Saudi Arabia.

Disclosure statement

No potential conflict of interest was reported by the authors.

Data availability statement

All data relevant to the study are included in the article.

Author contributions

Conceptualization, LM; methodology, MA, LM, AA; validation, SAO, LM; investigation, MA, LM, AA and SAO.; resources, LM and SA; data curation, MA and LM.; writing original draft preparation, LM and MA; supervision LM and SA. All authors have read and agreed to the published version of the manuscript.

Institutional review board statement

The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Institutional Review Board of the Ethic Committee of King Saud University under the number, 21-6508 and dated 05 April 2022.

Informed consent statement

Informed consent was obtained from all subjects involved in the study.

Correction Statement

This article has been corrected with minor changes. These changes do not impact the academic content of the article.