文章：

植物血凝素诱导的全血IL2 mRNA可预测硼替佐米诱导的多发性骨髓瘤患者周围神经病变

Phytohemagglutinin-induced IL2 mRNA in whole blood can predict bortezomib-induced peripheral neuropathy for multiple myeloma patients

原文发布日期：2013-10-04

DOI: 10.1038/bcj.2013.47

类型: Original Article

开放获取: 是

英文摘要：

The proteasome inhibitor bortezomib has revolutionized the treatment of multiple myeloma. However, bortezomib-induced peripheral neuropathy (BiPN) is a serious complication that compromises clinical outcome. If patients with a risk of developing BiPN could be predicted, physicians might prefer weekly, reduced-dose, or subcutaneous approaches. To seek biomarkers for BiPN, we conducted a multicenter prospective study using a simple and unique system. Multiple myeloma patients received twice-weekly or weekly 1.3 mg/m2 bortezomib intravenously, and a 2-ml sample of whole blood was obtained before treatment and 2–3 days and 1–3 weeks after the first dose. Induction of gene expression was then quantified by real-time PCR. Of a total of 64 enrolled patients, 53 patient samples qualified for mRNA analysis. The BiPN grade was associated with phytohemagglutinin-induced IL2, IFNG and TNFSF2, as well as with lipopolysaccharide-induced IL6 levels. More importantly, of the 19 patients showing a ⩾3-fold increase in phytohemagglutinin-induced IL2, 14 did not suffer from BiPN (73.7% prediction), whereas of the 34 patients with a <3-fold increase, 23 experienced BiPN (67.6% prediction). Therefore, we concluded that pretreatment of phytohemagglutinin-induced IL2 mRNA levels in whole blood serve as a promising biomarker for predicting BiPN, and this finding warrants validation in a larger study.

摘要翻译： 

蛋白酶体抑制剂硼替佐米已彻底改变多发性骨髓瘤的治疗格局。然而，硼替佐米诱导的周围神经病变（BiPN）作为严重影响临床预后的并发症，亟需有效防治策略。若能在治疗前识别BiPN高风险患者，临床医生可优先选择周疗方案、剂量调整或皮下给药等替代方案。为探索BiPN生物标志物，我们通过一套简易独创的系统开展多中心前瞻性研究。多发性骨髓瘤患者接受每周两次或一次1.3mg/m²静脉注射硼替佐米治疗，分别于治疗前、首次给药后2-3天及1-3周采集2ml全血样本，采用实时荧光定量PCR技术进行基因表达诱导定量分析。在64例入组患者中，53例样本符合mRNA分析要求。研究发现BiPN严重程度与植物血凝素诱导的IL2、IFNG、TNFSF2以及脂多糖诱导的IL6水平显著相关。尤为重要的是，在19例植物血凝素诱导IL2表达增幅≥3倍的患者中，14例未发生BiPN（预测准确率73.7%）；而在34例IL2表达增幅<3倍的患者中，23例出现BiPN（预测准确率67.6%）。由此得出结论：全血中植物血凝素诱导的IL2 mRNA预处理水平可作为预测BiPN的有前景的生物标志物，该发现尚需更大规模研究予以验证。

原文链接：

Phytohemagglutinin-induced IL2 mRNA in whole blood can predict bortezomib-induced peripheral neuropathy for multiple myeloma patients