Host immune genetic variations influence the risk of developing acute myeloid leukaemia: results from the NuCLEAR consortium
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Sanchez-Maldonado, J. M., Campa, D., Springer, J., Badiola, J., Niazi, Y., Moñiz-Díez, A., ... & Brezina, S. (2020). Host immune genetic variations influence the risk of developing acute myeloid leukaemia: results from the NuCLEAR consortium. Blood cancer journal, 10(7), 1-11. [https://doi.org/10.1038/s41408-020-00341-y]
SponsorshipAstella Pharma Inc.; Instituto de Salud Carlos III PI12/02688 PI17/02276; Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER) NORTE-01-0145-FEDER-000013; Portuguese Foundation for Science and Technology CEECIND/04601/2017 CEECIND/03628/2017; Astellas Pharmaceuticals
The purpose of this study was to conduct a two-stage case control association study including 654 acute myeloid leukaemia (AML) patients and 3477 controls ascertained through the NuCLEAR consortium to evaluate the effect of 27 immune-related single nucleotide polymorphisms (SNPs) on AML risk. In a pooled analysis of cohort studies, we found that carriers of the IL13rs1295686A/A genotype had an increased risk of AML (PCorr = 0.0144) whereas carriers of the VEGFArs25648T allele had a decreased risk of developing the disease (PCorr = 0.00086). In addition, we found an association of the IL8rs2227307 SNP with a decreased risk of developing AML that remained marginally significant after multiple testing (PCorr = 0.072). Functional experiments suggested that the effect of the IL13rs1295686 SNP on AML risk might be explained by its role in regulating IL1Ra secretion that modulates AML blast proliferation. Likewise, the protective effect of the IL8rs2227307 SNP might be mediated by TLR2-mediated immune responses that affect AML blast viability, proliferation and chemorresistance. Despite the potential interest of these results, additional functional studies are still warranted to unravel the mechanisms by which these variants modulate the risk of AML. These findings suggested that IL13, VEGFA and IL8 SNPs play a role in modulating AML risk.