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

机译:植物血凝素诱导的全血IL2 mRNA可以预测硼替佐米引起的多发性骨髓瘤患者的周围神经病变

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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 IL2 mRNA levels in whole blood serve as a promising biomarker for predicting BiPN, and this finding warrants validation in a larger study.
机译:蛋白酶体抑制剂硼替佐米彻底改变了多发性骨髓瘤的治疗方法。但是,硼替佐米引起的周围神经病(BiPN)是严重的并发症,损害了临床结果。如果可以预测有BiPN风险的患者,医生可能更喜欢每周一次,减少剂量或皮下途径。为了寻找BiPN的生物标志物,我们使用简单且独特的系统进行了多中心前瞻性研究。多发性骨髓瘤患者每周或每周两次接受硼替佐米1.3?mg / m 2 硼替佐米静脉注射,在治疗前以及治疗后2–3天和1-3周获得2 ml全血样本。第一剂。然后通过实时PCR定量基因表达的诱导。在总共64位患者中,有53位患者样本符合进行mRNA分析的条件。 BiPN等级与植物血凝素诱导的IL2,IFNG和TNFSF2以及脂多糖诱导的IL6水平相关。更重要的是,在19例显示植物血凝素诱导的IL2升高了3倍的患者中,有14例未患有BiPN(预测为73.7%),而在34例全血中IL2 mRNA水平高的患者中,它是有希望的生物标志物用于预测BiPN,这一发现值得在更大的研究中进行验证。

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