LEF1在成人急性淋巴细胞白血病中的突变和表达及其临床意义  

Mutation and Expression of LEF1 in Adult Acute Lymphocytic Leukemia and Their Clinical Significance

作　　者：刘娟[1] 郭星[1] 葛峥[1] 张闰[1] 许景艳[2] 李敏[1] 吴雨洁[1] 乔纯[1] 仇海荣[1] 张建富[1] 李建勇[1] 

机构地区：[1]南京医科大学第一附属医院,江苏省人民医院血液科,江苏南京210029 [2]南京大学医学院附属医院,南京市鼓楼医院血液科,江苏南京210008

出　　处：《中国实验血液学杂志》2014年第5期1212-1216,共5页Journal of Experimental Hematology

基　　金：国家自然科学基金面上项目(30973376,81270613,81370656);江苏省医学重点人才(RC2011077);中国博士后科学基金特别资助(201003598);中国博士后科学基金(20090461134);教育部"留学回国人员科研启动基金"(第39批);江苏省"六大人才高峰"资助(2010-WS-024);南京市留学回国人员科技活动项目择优资助(2009)

摘　　要：淋巴增强因子1(1ymphoid enhancer factor 1,LEF1)是Wingless-type(Wnt)信号通路中的重要转录因子。本研究旨在探讨成人急性淋巴细胞白血病(acute Lymphocytic Leukemia,ALL)中LEF1基因突变、表达特征及其临床意义。采用基因组DNA扩增、测序和荧光定量PCR等方法研究131例初发成人ALL患者中LEF1基因突变和表达,及其与临床预后参数和生存时间的相关性。结果显示,本组131例成人ALL患者中LEF1突变率3.1%(4/131),均为点突变(位于外显子2和3);初诊时外周血中位白细胞计数和中位原始幼稚淋巴细胞百分比在LEF1高表达组明显高于低表达组(70.6×109/L vs 26.2×109/L,P=0.010;81.0%vs 57.0%,P=0.014);费城染色体阳性ALL和高危患者比例LEF1高表达组显著高于低表达组(66.7%vs 36.5%,P=0.038;79.2%vs 56.2%,P=0.044)。结论:LEF1高表达在成人ALL的发病机制中可能具有重要意义。Lymphoid enhancer factor 1 （LEF1） is a key transcription factor in Wingless-type （Wnt） pathway.The present study was aimed to explore the genetic mutation and expression of LEF1,and their clinical significance in adult patients with acute lymphocytic leukemia （ALL）.Genomic DNA was amplified and sequenced to detect the mutation of LEF1 in 131 newly diagnosed adult patients with ALL.Quantitative PCR （qPCR） was performed to detect the expression of LEF1.Moreover,the correlations between mutations and expression of LEF1 with clinical characteristics were analyzed.The results showed that the frequency of LEF1 mutation in adult ALL was 3.1% （4/131）and all of them were point mutations located in exon 2 and 3 ; the median white blood cell c ount and median percentage of blasts at diagnosis were significantly higher in LEF1 high expression group than in low expression group（70.6 × 109/L vs 26.2 × 109/L） （P =0.010） ; （81.0% vs 57.0%） （P =0.014） ; in addition,the percentage of patients with Philadelphia chromosome positive and patients in high-risk group significantly increased in LEF1 high expression group compared with that in low expression group（66.7% vs 36.5%） （P =0.038） ; （79.2% vs 56.2%） （P =0.044）.It is concluded that high expression of LEF1 may play an important role on development of adult ALL.

关 键 词：LEF1 急性淋巴细胞白血病 基因突变 

分 类 号：R733.71[医药卫生—肿瘤]