微小RNA223在B淋巴增殖性疾病中的表达及其临床意义  

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

作　　者：周可树[1] 于珍[1] 易树华[1] 李增军[1] 安刚[1] 王燕婴 邹德慧[1] 齐军元[1] 赵耀中[1] 宋永平[2] 邱录贵[1] 

机构地区：[1]中国医学科学院北京协和医学院血液学研究所血液病医院实验血液学国家重点实验室,天津300020 [2]郑州大学附属肿瘤医院河南省肿瘤医院

出　　处：《中华医学杂志》2011年第34期2384-2387,共4页National Medical Journal of China

基　　金：卫生部临床学科重点项目（2010-2012）;天津市科技支撑计划（09ZCGYSF01000,09ZCZDSF03800）

摘　　要：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SPSS16．0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4．254-0．67，P=0．044）；（3）根据IgVH突变状态采用受试者工作特征（ROC）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microRNA-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。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 microPLNA-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 �

关 键 词：淋巴组织增殖性疾病 微RNAS 预后 

分 类 号：R551.2[医药卫生—血液循环系统疾病]