Grupo de Farmacogenética, Instituto Investigación Sanitaria La Fe and Área del Medicamento, Hospital Universitari i Politècnic, Valencia, Spain.
Servicio de Farmacia, Área del Medicamento. Hospital Universitari i Politècnic, Valencia, Spain.
Leuk Lymphoma. 2021 Mar;62(3):659-668. doi: 10.1080/10428194.2020.1839650. Epub 2020 Nov 2.
Anthracycline uptake could be affected by influx and efflux transporters in acute myeloid leukemia (AML). Combinations of single-nucleotide polymorphisms (SNPs) of wild-type genotype of influx transporters () and homozygous variant genotypes of polymorphisms (, , ) were evaluated in 225 adult AML patients. No differences in complete remission were reported, but higher induction death was observed with combinations of rs4149056 and (triple variant haplotype, rs1128503), previously associated with and SNPs. Several combinations of and with SNPs were associated with higher toxicities, including nephrotoxicity and hepatotoxicity, neutropenia, previously related to , and a novel correlation with mucositis. Combination of rs714368 and rs2231142 was related to cardiac toxicity, reproducing previous correlations with . This study shows the impact of transporter polymorphisms in AML chemotherapy safety. Further prospective studies with larger populations are needed to validate these associations.
蒽环类药物摄取可能受急性髓系白血病（AML）中流入和流出转运蛋白的影响。在 225 名成年 AML 患者中评估了流入转运蛋白野生型基因型（）和单核苷酸多态性（SNP）纯合变异基因型（、、）的组合。尽管报道称完全缓解率没有差异，但先前与和 SNPs 相关的 rs4149056 和（三重变体单倍型，rs1128503）组合观察到诱导死亡更高。与 SNPs 的和与先前与和相关的中性粒细胞减少症、肾毒性和肝毒性等毒性较高的多种组合有关，以及与粘膜炎的新相关性。rs714368 和 rs2231142 的组合与心脏毒性相关，再现了与的先前相关性。本研究表明转运蛋白多态性对 AML 化疗安全性的影响。需要进一步进行具有更大人群的前瞻性研究来验证这些关联。
