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微小 RNA-223 的表达在 B 细胞淋巴增殖性疾病中普遍下调,与慢性淋巴细胞白血病患者的不良生存相关。

MicroRNA-223 expression is uniformly down-regulated in B cell lymphoproliferative disorders and is associated with poor survival in patients with chronic lymphocytic leukemia.

机构信息

Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences, Tianjin, China.

出版信息

Leuk Lymphoma. 2012 Jun;53(6):1155-61. doi: 10.3109/10428194.2011.642303. Epub 2012 Jan 31.

Abstract

MicroRNA-223 (miR-223) expression has been demonstrated to be stage-specific in B cell differentiation and associated with the outcome of chronic lymphocytic leukemia (CLL). However, the expression pattern of miR-223 in B cell lymphoproliferative disorders and its association with the outcome of Chinese patients with CLL have not been investigated. In this study, we demonstrated that miR-223 expression was significantly decreased in CLL, mantle cell lymphoma (MCL) and splenic marginal zone lymphoma (SMZL). In CLL, miR-223 expression decreased significantly with progression from early to advanced clinical stages and was significantly lower in patients with elevated β(2)-microglobulin, unmutated immunoglobulin variable heavy chain (IgVH) gene or with disease progression or death. Using a cut-off determined by receiver operating characteristic (ROC) analysis optimizing concordance with IgVH mutational status, miR-223-negative and -positive groups were defined for 22 and 31 patients, respectively. The median progression-free survival (PFS) and overall survival of the miR-223-negative group were 13 and 40 months, respectively, significantly shorter than for the miR-223-positive group (both not reached; p = 0.002 and p = 0.018, respectively). Multivariate analysis revealed that the absence of miR-223 was the only independent factor capable of predicting shorter PFS. In conclusion, miR-223 is uniformly down-regulated in B-LPDs and is a useful prognostic factor for patients with CLL.

摘要

miR-223(miR-223)的表达在 B 细胞分化中具有阶段特异性,并且与慢性淋巴细胞白血病(CLL)的结果相关。然而,miR-223 在 B 细胞淋巴增殖性疾病中的表达模式及其与中国 CLL 患者的结果的关系尚未得到研究。在这项研究中,我们证明 miR-223 的表达在 CLL、套细胞淋巴瘤(MCL)和脾边缘区淋巴瘤(SMZL)中显著降低。在 CLL 中,miR-223 的表达随着从早期到晚期临床阶段的进展而显著降低,并且在β2-微球蛋白升高、未突变免疫球蛋白重链可变区(IgVH)基因或疾病进展或死亡的患者中显着降低。使用通过接收器操作特性(ROC)分析确定的截止值来优化与 IgVH 突变状态的一致性,将 miR-223-阴性和阳性组分别定义为 22 和 31 例患者。miR-223-阴性组的中位无进展生存期(PFS)和总生存期分别为 13 和 40 个月,明显短于 miR-223-阳性组(均未达到;p=0.002 和 p=0.018)。多变量分析显示,miR-223 的缺失是唯一能够预测较短 PFS 的独立因素。总之,miR-223 在 B-LPDs 中均匀下调,是 CLL 患者的有用预后因素。

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