文章：

一种用于检测多发性骨髓瘤中多重耐药性和疾病负荷的液体活检

A liquid biopsy to detect multidrug resistance and disease burden in multiple myeloma

原文发布日期：2020-03-13

DOI: 10.1038/s41408-020-0304-7

类型: Article

开放获取: 是

英文摘要：

Multiple myeloma is an incurable cancer of bone marrow plasma cells, with a 5-year survival rate of 43%. Its incidence has increased by 126% since 1990. Treatment typically involves high-dose combination chemotherapy, but therapeutic response and patient survival are unpredictable and highly variable—attributed largely to the development of multidrug resistance (MDR). MDR is the simultaneous cross-resistance to a range of unrelated chemotherapeutic agents and is associated with poor prognosis and survival. Currently, no clinical procedures allow for a direct, continuous monitoring of MDR. We identified circulating large extracellular vesicles (specifically microparticles (MPs)) that can be used to monitor disease burden, disease progression and development of MDR in myeloma. These MPs differ phenotypically in the expression of four protein biomarkers: a plasma-cell marker (CD138), the MDR protein, P-glycoprotein (P-gp), the stem-cell marker (CD34); and phosphatidylserine (PS), an MP marker and mediator of cancer spread. Elevated levels of P-gp+ and PS+ MPs correlate with disease progression and treatment unresponsiveness. Furthermore, P-gp, PS and CD34 are predominantly expressed in CD138− MPs in advanced disease. In particular, a dual-positive (CD138−P-gp+CD34+) population is elevated in aggressive/unresponsive disease. Our test provides a personalised liquid biopsy with potential to address the unmet clinical need of monitoring MDR and treatment failure in myeloma.
 

摘要翻译： 

多发性骨髓瘤是一种无法治愈的骨髓浆细胞恶性肿瘤，五年生存率为43%。自1990年以来，其发病率增加了126%。标准治疗方案通常采用大剂量联合化疗，但治疗反应和患者生存期存在高度不可预测性和个体差异性——这主要归因于多药耐药性的产生。多药耐药性指对多种结构不相关化疗药物同时产生交叉耐药的现象，与患者不良预后和生存期缩短密切相关。目前临床尚缺乏能够直接、持续监测多药耐药性的技术手段。我们鉴定出循环大型细胞外囊泡（主要是微颗粒）可作为监测骨髓瘤疾病负荷、进展及多药耐药性发展的生物标志物。这些微颗粒在四种蛋白生物标志物的表达上呈现表型差异：浆细胞标志物CD138、多药耐药蛋白P-糖蛋白、干细胞标志物CD34，以及作为微颗粒标志物和癌症转移介导物的磷脂酰丝氨酸。其中P-糖蛋白阳性和磷脂酰丝氨酸阳性微颗粒水平升高与疾病进展及治疗无应答相关。在晚期患者中，P-糖蛋白、磷脂酰丝氨酸和CD34主要表达于CD138阴性微颗粒。特别值得注意的是，在侵袭性/难治性病例中CD138阴性/P-糖蛋白阳性/CD34阳性三标记阳性群体显著增加。本研究开发的检测方法可实现个性化液体活检，有望解决骨髓瘤多药耐药性与治疗失败监测这一临床未满足的需求。

原文链接：

A liquid biopsy to detect multidrug resistance and disease burden in multiple myeloma