Effect of single-nucleotide polymorphism in SLCO1B1 and CDA genes on response and toxicity of induction chemotherapy in acute myeloid leukemia

Abstract

Abstract Introduction Acute myeloid leukemia (AML) is a heterogeneous disease marked by clonal growth of myeloblasts in the bone marrow and peripheral circulation, leading to inefficient hematopoiesis and bone marrow failure. Single-nucleotide polymorphisms (SNPs) in genes involved in the metabolism of gold standard drugs used in AML treatment influence treatment-related toxicities, response, and survival. Aim To study SNP rs (532545) of the CDA gene and SNP rs(2291075) of the SLCO1B1 gene in newly diagnosed adults with AML. Patients and methods The study included 75 newly diagnosed adult patients with AML admitted to Alexandria Main University Hospital in the period between November 2020 and December 2021. Clinical data and bone marrow samples were obtained. Molecular genetic analysis involving CDA and SLCO1B1 single-nucleotide gene polymorphisms was done using PCR-restriction fragment length polymorphism-coupled analys real time PCR. Results The mean age was 40.3 ± 13.12 years. After induction chemotherapy with a 3 + 7 protocol, 29 (38.7%) patients achieved complete remission. Patients with homozygous variant T/T of SLCO1B1 gene had a lower risk of treatment-related anemia in comparison with C/T and C/C genotypes (P<0.001). The heterozygous C/T variant of the CDA gene rs (532545) had better relapse-free survival and overall survival when compared with the C/C and T/T genotypes, respectively. No statistically significant correlation between CDA and SLCO1B1 single-nucleotide gene polymorphisms and postinduction treatment response was found. Conclusion Polymorphisms in SLCO1B1 and CDA genes involved in chemotherapy metabolism pathways can be useful in assessment of treatment-related toxicities and overall survival.