Genetic Variants of ABC and SLC Transporter Genes and Chronic Myeloid Leukaemia: Impact on Susceptibility and Prognosis

Solute carrier (SLC) and ATP-binding cassette (ABC) transporters comprise a variety of proteins expressed on cell membranes responsible for intrusion or extrusion of substrates, respectively, including nutrients, xenobiotics, and chemotherapeutic agents. These transporters mediate the cellular disposition of tyrosine kinase inhibitors (TKIs), and their genetic variants could affect its function, potentially predisposing patients to chronic myeloid leukaemia (CML) and modulating treatment response. We explored the impact of genetic variability (single nucleotide variants-SNVs) of drug transporter genes (, , , and ) on CML susceptibility, drug response, and mutation status. We genotyped 10 SNVs by tetra-primers-AMRS-PCR in 198 CML patients and 404 controls, and assessed their role in CML susceptibility and prognosis. We identified five SNVs associated with CML predisposition, with some variants increasing disease risk, including TT genotype (rs1045642), and others showing a protective effect (GG genotype rs274558). We also observed different haplotypes and genotypic profiles associated with CML predisposition. Relating to drug response impact, we found that CML patients with the CC genotype (rs2231142 ) had an increased risk of TKI resistance (six-fold). Additionally, CML patients carrying the CG genotype (rs683369 ) presented a 4.54-fold higher risk of mutations. Our results suggest that drug transporters' SNVs might be involved in CML susceptibility and TKI response, and predict the risk of mutations, highlighting the impact that SNVs could have in therapeutic selection.