Division of Pharmacy Practice and Science, College of Pharmacy, The Ohio State University, Columbus, OH, U.S.A.
Comprehensive Cancer Center, The Ohio State University, Columbus, OH, U.S.A.
Anticancer Res. 2022 Jan;42(1):385-395. doi: 10.21873/anticanres.15497.
It has been reported that expression of OCT3 enhanced the sensitivity to melphalan in cells, indicative of potential roles of OCT3 in melphalan transport. Herein we investigated the association of select single nucleotide polymorphisms in SLC22A3 (gene encoding OCT3) with clinical outcomes in multiple myeloma (MM) patients with hematopoietic autologous stem cell transplants followed by high-dose melphalan therapy.
Melphlan concentrations in blood samples from 108 MM patients were measured using liquid chromatography-tandem mass spectrometry (LC-MS/ΜS); genotypes of rs2048327, rs1810126, and rs3088442 in these patients were determined using quatitive RT-PCR assays.
Rs3088442 A variant-carriers had a significantly increased risk of severe oral mucositis in comparison with homozygous rs3088442 G-carriers with adjusted odds ratio of 4.00 (95% CI=1.25-14.7; p=0.027). Rs3088442 A carriers tended to have lower creatinine clearance (p=0.10) and higher maximum plasma concentration of melphalan (p=0.07).
OCT3 might be involved in melphalan transport in MM patients.
有报道称，OCT3 的表达增强了细胞对美法仑的敏感性，这表明 OCT3 在美法仑转运中可能发挥作用。在此，我们研究了 SLC22A3（编码 OCT3 的基因）中选定的单核苷酸多态性与接受大剂量美法仑治疗的多发性骨髓瘤（MM）患者造血自体干细胞移植后的临床结局之间的关系。
采用液相色谱-串联质谱法（LC-MS/MS）测定 108 例 MM 患者血样中的美法仑浓度；采用定量 RT-PCR 法测定这些患者中 rs2048327、rs1810126 和 rs3088442 的基因型。
与 rs3088442 纯合 GG 携带者相比，rs3088442 A 变异携带者发生严重口腔黏膜炎的风险显著增加，校正后的优势比为 4.00（95%CI=1.25-14.7；p=0.027）。rs3088442 A 携带者倾向于具有较低的肌酐清除率（p=0.10）和较高的美法仑最大血浆浓度（p=0.07）。
OCT3 可能参与 MM 患者美法仑的转运。
