Abstract：
Multiple myeloma (MM) is a prevalent yet incurable hematologic malignancy. Despite the proven efficacy of proteasome inhibitors in treating MM, resistance to Bortezomib-based treatments persists in a subset of patients. This case control study explores the potential of circulating endothelial progenitor cells (EPCs) as biomarkers for predicting response to Proteasome Inhibitor based therapy combined with Dexamethasone in MM patients. This study was conducted on 105 MM patients receiving bortezomib plus dexamethasone therapy and 90 healthy individuals as a control group. Utilizing 8-color multi-parameter flow cytometry, we assessed the levels of circulating EPCs, identified through CD34 FITC and CD309 PE markers at diagnosis and after one treatment cycle (4 weeks). Our findings revealed that patients exhibiting poor response to therapy showed significantly higher CD34/CD309 values than those with a good response (p < 0.001). The delineation of response based on CD34/CD309 expression was established with a cutoff ≤ 0.9 for percentage (yielding 100% sensitivity and 94.1% specificity) and ≤ 12.5 for absolute value (also with 100% sensitivity and 94.1% specificity). These results underscore the potential of EPC population levels, as quantified by CD34/CD309, to serve as a predictive biomarker for immunomodulatory treatment in MM patients undergoing Proteasome Inhibitor and Dexamethasone therapy.
摘要：
多发性骨髓瘤（MM）是一种普遍但无法治愈的血液系统恶性肿瘤。尽管蛋白酶体抑制剂在治疗MM方面的疗效已得到证实，部分患者对硼替佐米治疗的耐药性持续存在。这项病例对照研究探讨了循环内皮祖细胞（EPCs）作为预测MM患者对基于蛋白酶体抑制剂的治疗联合地塞米松的反应的生物标志物的潜力。这项研究是对105例接受硼替佐米加地塞米松治疗的MM患者和90例健康个体作为对照组进行的。利用8色多参数流式细胞术，我们评估了循环EPC的水平，在诊断时和一个治疗周期（4周）后，通过CD34FITC和CD309PE标志物鉴定。我们的发现表明，对治疗反应较差的患者显示出明显高于反应良好的患者的CD34/CD309值（p<0.001）。建立基于CD34/CD309表达的反应描述,其中对于百分比(产生100%灵敏度和94.1%特异性)的截止值≤0.9,对于绝对值(也具有100%灵敏度和94.1%特异性)的截止值≤12.5。这些结果强调了EPC人口水平的潜力，通过CD34/CD309定量，作为接受蛋白酶体抑制剂和地塞米松治疗的MM患者免疫调节治疗的预测生物标志物。
