Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences, Tianjin, China.
Leuk Lymphoma. 2012 Jun;53(6):1155-61. doi: 10.3109/10428194.2011.642303. Epub 2012 Jan 31.
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.
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。