Phytohemagglutinin-induced IL2 mRNA in whole blood can predict bortezomib-induced peripheral neuropathy for multiple myeloma patients.
Phytohemagglutinin-induced IL2 mRNA in whole blood can predict bortezomib-induced peripheral neuropathy for multiple myeloma patients.
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DOI：
10.1038/bcj.2013.47
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发表时间：
2013-10-04
影响因子：
12.8
通讯作者：
Kizaki, M.
中科院分区：
文献类型：
--
作者：
Watanabe, T.;Mitsuhashi, M.;Sagawa, M.;Ri, M.;Suzuki, K.;Abe, M.;Ohmachi, K.;Nakagawa, Y.;Nakamura, S.;Chosa, M.;Iida, S.;Kizaki, M.
蛋白酶体抑制剂Bortezomib使多发性骨髓瘤的治疗发生了革命性的变化。然而，Bortezomib诱导的周围神经病变(BiPN)是一种严重的并发症，影响临床结果。如果可以预测有发生BiPN风险的患者，医生可能更倾向于每周、减少剂量或皮下注射。为了寻找BiPN的生物标志物，我们使用一种简单而独特的系统进行了一项多中心前瞻性研究。多发性骨髓瘤患者每周2次或每周2次静脉滴注硼替佐米1.3 mg/m2，分别于治疗前、治疗后2~3天和1~3周采全血2ml。然后用实时定量聚合酶链式反应(Real-time PCR)对基因表达的诱导进行量化。在登记的全部患者中，有53例患者样本符合基因分析条件。BiPN分级与植物血凝素诱导的IL2、IFNG和TNFSF2以及内毒素诱导的IL6水平相关。更重要的是，在植物血凝素诱导的IL2增加3倍的19名患者中，14名患者没有发生⩾(73.7%预测)，而在34名增加3倍的患者中，23名患者发生了BPN(67.6%预测)。因此，我们得出结论，植物血凝素诱导的全血IL2mRNA水平的预处理是预测BiPN的一个有前景的生物标志物，这一发现值得在更大规模的研究中验证。
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.
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影响因子：
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作者：
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