SLC29A1 (ENT1) polymorphisms and outcome of complete remission in acute myeloid leukemia

Abstract

The solute carrier family 29 (equilibrative nucleoside transporter), member 1 (SLC29A1) is known to be involved in the transportation and resistance of the nucleoside analog cytosine arabinoside (AraC), one of the most effective drugs in the treatment of acute myeloid leukemia (AML). In vitro functional analysis in AML cells and genetic association study were performed. Our functional analysis of SLC29A1 on anticancer effects of AraC showed that cytotoxic effects of AraC in AML cell lines were decreased by the reduction of SLC29A1 expression (P < 0.05). To investigate whether SLC29A1 polymorphisms could affect the achievement of complete remission (CR) in AML, we genotyped a total of six common single nucleotide polymorphisms on SLC29A1 in 103 AML patients, including 17 successes and 86 failures in CR. As a result, rs3734703 in 3'-untranslated region was significantly associated with CR even after correction for multiple testing (Fisher's exact test, P = 0.008; P (corr) = 0.04). A haplotype, ht3 (A-G-G-T-C-A; frequency = 0.294 in success group; frequency = 0.120 in failure group), also revealed a significant association with CR (P = 0.01; simulated P (sim) = 0.02). Although further replication in larger subjects and further functional evaluations are required, our results suggest the contribution of SLC29A1 to cytotoxic effects of AraC. In addition, genetic variations of SLC29A1 could be a potential marker for the achievement of CR of cancers of white blood cells including AML.