Immune checkpoint‐related gene polymorphisms are associated with acute myeloid leukemia

Abstract

BackgroundChemotherapy is still the standard regimen for treating acute myeloid leukemia (AML) and its disappointing efficacy requires the urgent need for new therapeutic targets. It is well known that immune response plays an increasingly significant role in the pathogenesis of AML.MethodsWe detected nine single nucleotide polymorphisms (SNPs) in immune checkpoint‐related genes, including PD1, LAG3, TIM3, and TIGIT in 285 AML inpatients and 324 healthy controls. SNP genotyping was performed on the MassARRAY platform. Furthermore, we analyzed the relationship between the susceptibility and prognosis of AML and the selected SNPs.ResultsOur results showed that rs2227982 and rs10204525 in PD1 were significantly associated with susceptibility to AML after false discovery rate correction. PD1 rs10204525 also showed a significant correlation with the response to chemotherapy and risk stratification of AML. Importantly, the AA genotype of PD1 (rs2227982) under the recessive model showed a negative impact on AML prognosis independently.ConclusionsOur results indicate that PD1 SNPs are important for susceptibility and prognosis in AML, which may provide a new therapeutic target for AML patients.

Associations of PD-1 and PD-L1 gene polymorphisms with cancer risk: a meta-analysis based on 50 studies

“…Interestingly, the PD-1.9 polymorphism is located at position +7625 in exon 5, which causes C to T substitution in extra cellular domain of PD-1 receptor during protein synthesis, affecting the sequence, resulting in alteration of structural and practical variations of PD-1 [ 29 , 85 ]. For instance, variants in other undetected coinhibitory molecules, such as CD28 and lymphocyte activating 3 (LAG3) could affect the PD-1.9 function [ 76 ]. Additionally, PD-1.9 variant was found to be remarkably related to high expression of Her-2, showing that the genotype may regulate expression of oncogenes in occurrence and development of cancer [ 51 ].…”

Association of genetic predisposition studies in CYP1A1 polymorphism studies in acute myeloid leukemia

“…There has been an abundance of research into the causes of this condition, but scientists still don't fully understand the biochemical processes at play here ( Ahadi et al, 2022 ). Humans have many genetic variations, the most frequent of which are single nucleotide polymorphisms (SNPs), which are being shown to have an increasingly essential role in human diseases ( Wu et al, 2023 ). Numerous SNPs in a broad variety of genes have been linked to an increased risk of AML by genome-wide association studies (GWAS).…”