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下调的miR-33b是一种与多发性骨髓瘤疾病进展和不良预后相关的新型预测指标。

Downregulated miR-33b is a novel predictor associated with disease progression and poor prognosis in multiple myeloma.

作者信息

Li Fei, Hao Mu, Feng Xiaoyan, Zang Meirong, Qin Yu, Yi Shuhua, Li Zengjun, Xu Yan, Zhou Lili, Sui Weiwei, Deng Shuhui, Zou Dehui, Zhan Fenghuang, Qiu Lugui

机构信息

State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China; Department of Hematology, The First Affiliated Hospital of Nanchang University, NanChang 330006, China.

State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China.

出版信息

Leuk Res. 2015 Jul;39(7):793-9. doi: 10.1016/j.leukres.2015.04.010. Epub 2015 Apr 25.

Abstract

MiRNAs located at chromosome fragile sites play important roles in regulating critical genes associated with myeloma pathogenesis, disease progression and drug resistance. Our previous results have identified miR-33b (located in chromosome 17p) was one of the dysregulated miRNAs in the sera of newly diagnosed MM patients. However, little is known about its expression pattern in myeloma tumor cells and its prognostic value in MM patients. In the present study, we investigated the expression pattern of miR-33b in 58 newly diagnosed, 11 relapsed, 12 remission MM patients and 18 health donors by quantitative real-time PCR. Our results showed the expression of miR-33b was obviously down-regulated in newly diagnosed and relapsed MM patients compared to remission patients and health donors (p<0.001). Moreover, patients with del(13q), del(17p), t(4;14) and high-risk genetic abnormalities have lower expression levels of miR-33b compared to patients without those of abnormalities (p=0.032, 0.018, 0.034, 0.005). Survival analysis showed patients with miR-33b low expression had significantly shortened PFS (p=0.016) and OS (p=0.033) and might be associated with drug resistance to bortezomib-based treatment. Our data suggest that down-regulated miR-33b might be a novel predictor associated with disease progression and poor prognosis in MM.

摘要

位于染色体脆弱位点的微小RNA在调控与骨髓瘤发病机制、疾病进展和耐药性相关的关键基因中发挥着重要作用。我们之前的研究结果已确定miR-33b(位于17号染色体短臂)是新诊断的骨髓瘤患者血清中失调的微小RNA之一。然而,关于其在骨髓瘤肿瘤细胞中的表达模式及其在骨髓瘤患者中的预后价值知之甚少。在本研究中,我们通过定量实时聚合酶链反应调查了58例新诊断、11例复发、12例缓解期的骨髓瘤患者以及18名健康供体中miR-33b的表达模式。我们的结果显示,与缓解期患者和健康供体相比,新诊断和复发的骨髓瘤患者中miR-33b的表达明显下调(p<0.001)。此外,与没有这些异常的患者相比,存在13号染色体长臂缺失(del(13q))、17号染色体短臂缺失(del(17p))、4号与14号染色体易位(t(4;14))和高危基因异常的患者miR-33b表达水平较低(p=0.032、0.018、0.034、0.005)。生存分析表明,miR-33b低表达的患者无进展生存期(PFS)显著缩短(p=0.016),总生存期(OS)也显著缩短(p=0.033),并且可能与对硼替佐米为基础的治疗产生耐药性有关。我们的数据表明,miR-33b表达下调可能是与骨髓瘤疾病进展和不良预后相关的一个新的预测指标。

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