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循环 miR-146a 表达预测成人慢性髓性白血病对伊马替尼的早期治疗反应。

Circulating miR-146a expression predicts early treatment response to imatinib in adult chronic myeloid leukemia.

机构信息

Clinical Pathology, Kafr el-Sheikh University, Kafr el-Sheikh, Egypt

Clinical Pathology, Kafr el-Sheikh University, Kafr el-Sheikh, Egypt.

出版信息

J Investig Med. 2021 Feb;69(2):333-337. doi: 10.1136/jim-2020-001563. Epub 2020 Nov 10.

Abstract

This study aimed to investigate the prognostic role of circulating miR-146a in the prediction of early response to imatinib treatment in patients with chronic myeloid leukemia (CML). Sixty patients with CML and 20 healthy controls were recruited in this study. was assessed by quantitative rt-PCR at days 0 and 90 of imatinib therapy. Circulating miR-146a levels were assessed by quantitative rt-PCR at days 0, 14 and 90 of imatinib therapy for patients and once for controls. At day 90 of treatment, treatment response was achieved in 48 patients (80.0%). Responders had significantly lower baseline Sokal score when compared with non-responders. They also had significantly lower expression at day 90 of treatment. The circulating miR-146a level was significantly lower in patients with CML than in healthy subjects and showed a significant rise after 14 days of imatinib treatment and an inverse correlation with expression levels at 90 days. Using multivariate logistic regression analysis, baseline ) (OR (95% CI) 1.09 (1.03 to 1.016), p=0.006) and miR-146a at 14 days (OR (95% CI) 0.002 (0.0 to 0.09), p=0.001) were significant predictors of treatment response. Using ROC curve analysis, it was found that miR-146a expression at 14 and 90 days could distinguish responders from non-responders (AUC (95% CI) 0.849 (0.733 to 0.928) and 0.867 (0.755 to 0.941), respectively). This study reported for the first time that measurement of the circulating miR-146a expression at 14 days can predict the early response to imatinib treatment in patients with CML. Thus, this work indicates that miR-146a should be investigated in the setting of treatment response to other tyrosine kinase inhibitors.

摘要

本研究旨在探讨循环 miR-146a 在预测慢性髓性白血病(CML)患者伊马替尼治疗早期反应中的预后作用。本研究纳入了 60 例 CML 患者和 20 名健康对照者。在伊马替尼治疗的第 0 天和第 90 天,通过定量 rt-PCR 评估 miR-146a 的表达。通过定量 rt-PCR 评估患者在伊马替尼治疗的第 0、14 和 90 天以及对照组单次的循环 miR-146a 水平。在治疗的第 90 天,48 例患者(80.0%)获得治疗应答。与无应答者相比,应答者的基线 Sokal 评分显著较低。他们在治疗第 90 天的表达也显著较低。与健康受试者相比,CML 患者的循环 miR-146a 水平显著降低,在接受伊马替尼治疗 14 天后显著升高,并与 90 天的表达水平呈负相关。使用多变量逻辑回归分析,基线 miR-146a(优势比(95%可信区间)1.09(1.03 至 1.016),p=0.006)和第 14 天的 miR-146a(优势比(95%可信区间)0.002(0.0 至 0.09),p=0.001)是治疗应答的显著预测因子。通过 ROC 曲线分析发现,第 14 天和第 90 天的 miR-146a 表达可以区分应答者和无应答者(曲线下面积(95%置信区间)分别为 0.849(0.733 至 0.928)和 0.867(0.755 至 0.941))。本研究首次报道,测量循环 miR-146a 的表达在第 14 天可以预测 CML 患者对伊马替尼治疗的早期反应。因此,这项工作表明,miR-146a 应该在酪氨酸激酶抑制剂治疗反应的背景下进行研究。

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