微小RNA223在B淋巴增殖性疾病中的表达及其临床意义

目的 检测微小RNA (microRNA) 223在我国常见B淋巴增殖性疾病中的表达并分析其临床意义。方法 2003至2010年中国医学科学院血液病医院慢性淋巴细胞白血病(CLL)53例,套细胞淋巴瘤(MCL) 13例,脾边缘区淋巴瘤(SMZL)9例,健康对照12名。取外周血（78例）或骨髓（9例）,常规分离单个核细胞并行CD19磁珠分选。提取CD19+B淋巴细胞的总RNA,应用TaqMan 探针法检测microRNA-223的表达。收集患者临床资料,应用SPSS 16.0软件进行统计学分析。结果 (1) microRNA-223的表达在CLL、MCL及SMZL分别为：4.58±0.62、4.03±0.54、4.63±0.57,显著低于健康对照(5.69±0.60,P＜0.01);microRNA-223在MCL的表达显著低于CLL及SMZL(P＜0. 05),而其在CLL与SMZL之间表达差异无统计学意义（P＞0.05）;(2)CLL患者microRNA-223的表达随疾病进展下调;CLL中IgVH未突变患者microRNA-223的表达水平显著低于IgVH突变患者（4. 05±0.69比4.67±0.51,P=0. 003）;microRNA-223在13q-阳性患者的表达显著高于13q-阴性患者（4. 76±0.45比4.25±0.67,P=0. 044）;(3)根据IgVH突变状态采用受试者工作特征(ROG)曲线方法,将microRNA-223的表达分为阳性组及阴性组。microRNA-223阳性组患者的中位疾病无进展生存(PFS)时间为48个月,高于microRNA-223阴性组的9个月(P =0.001),microRNA-223阳性组患者截至随访结束,无一例死亡。结论 micmRNA-223可能在B淋巴增殖性疾病的发病中起重要作用;其与患者预后相关,可能是CLL新的较为可靠的预后指标。

Expression of microRNA-223 and its clinical value in B lymphoproliferative disorders

Objective To detect the expression of microRNA-223 and analyze its clinical value in B lymphoproliferative disorders. Methods Peripheral blood samples ( n = 78) and bone marrow samples ( n =9 ) were collected from patients with chronic lymphocytic leukemia ( CLL, n = 53 ), mantle cell lymphoma ( MCL, n = 13 ), splenic marginal zone lymphoma ( SMZL, n = 9) and healthy donors ( n = 12) at our hospital from 2003 to 2010. Mononuclear cells were isolated and B cells purified with a CD19 + magneticbead system. Total RNA was extracted from purified CD19 + cells and the expression of microRNA-223 measured by TaqMan microRNA quantitative polymerase chain reaction (PCR). The clinical data of these patients were collected and their outcomes analyzed with SPSS 16. 0 software. Results ( 1 ) The levels of microRNA-223 in CLL, MCL and SMZL were 4. 58 ±0. 62, 4. 03 ±0. 54 and 4. 63 ±0. 57 respectively. And they were significantly lower than that in normal B cells ( 5.69 ± 0. 60, P ＜ 0. 01 ). The expression of microRNA-223 decreased significantly in MCL versus CLL and SMZL( P ＜0. 05 ). There was no statistical difference between CLL and SMZL( P ＞ 0. 05 ). (2) The down-regulation of microRNA-223 was associated with disease aggressiveness in CLL. Patients with unmutated immunoglobulin heavy chain variable region ( IgVH ) expressed significantly a lower level of microRNA-223 (4. 05 ± 0. 69 vs 4. 67 ± 0. 51, P = 0. 003 ).In 13q-negative patients, the expression of microRNA-223 decreased more significantly than that in 13q-positive patients (4. 25 ± 0. 67 vs 4. 76 ± 0. 45, P = 0. 044 ). ( 3 ) Using receiver operating characteristic (ROC) curve analysis, the microRNA-223 cutoffs were defined according to the IgVH mutational status. The patients were divided into the positive and negative subgroups. The median progression-free survival (PFS) of microRNA-223 positive patient subgroup was 48 months. It was significantly longer than the negative subgroup ( P = 0. 001 ). In the microRNA-223 positive subgroup, no patient died at the end of follow-up. ConclusionsMicroRNA-223 may play an important role in the pathogenesis of B lymphoproliferative disorders. The down-regulation of microRNA-223 is associated with disease aggressiveness and poor prognostic factors in CLL. It may become a new reliable prognostic predictor.