Haemato-Oncology Laboratory, Department of Haematology, Belfast HSC Trust, Belfast City Hospital, Belfast, Northern Ireland, UK.
Leuk Res. 2011 Nov;35(11):1457-63. doi: 10.1016/j.leukres.2011.05.033. Epub 2011 Jun 25.
Multi-drug resistance (MDR) leads to impaired treatment efficacy in all forms of malignancy. The main forms of MDR are thought to be mediated by the substrate transporting actions of certain adenosine triphosphate binding cassette (ABC) transport proteins. The genes ABCB1, ABCB4, ABCC1, ABCG2 and LRP1 have been identified as the most prominent contributors to clinically significant MDR. To date, no study has investigated the expression of these genes in plasma cell myeloma (PCM), or attempted to relate their expression to the incidence of relapse and/or stage at presentation. Here, we show that ABCB4 may be a prominent mediator of tumour cell MDR within PCM. Additionally, there are three SNPs (rs1045642, rs2032582 and rs1128503) within the most widely studied of these genes, ABCB1, which have been suggested to have a potential impact on OS in PCM and which may form a haplotype in ABCB1. rs1045642 in ABCB1 appears to be the only SNP affecting OS within the PCM patients studied, with minimal linkage disequilibrium demonstrated between it and rs2032582 and rs1128503.
多药耐药（MDR）导致所有形式的恶性肿瘤治疗效果受损。MDR 的主要形式被认为是由某些三磷酸腺苷结合盒（ABC）转运蛋白的底物转运作用介导的。ABCB1、ABCB4、ABCC1、ABCG2 和 LRP1 基因已被确定为对临床显著 MDR 的最重要贡献者。迄今为止，尚无研究调查这些基因在浆细胞瘤（PCM）中的表达情况，也未尝试将其表达与复发率和/或发病时的分期相关联。在这里，我们表明 ABCB4 可能是 PCM 中肿瘤细胞 MDR 的主要介导者。此外，在这些基因中研究最广泛的 ABCB1 中存在三个 SNP（rs1045642、rs2032582 和 rs1128503），有人认为它们可能对 PCM 中的 OS 有潜在影响，并且它们可能在 ABCB1 中形成单倍型。ABCB1 中的 rs1045642 似乎是影响所研究的 PCM 患者 OS 的唯一 SNP，它与 rs2032582 和 rs1128503 之间显示出最小的连锁不平衡。
