PAX5基因在成人急性淋巴细胞白血病中的突变和表达特征研究  

Mutation and Expression of PAX5 Gene in Adult Acute Lymphoblastic Leukemia

作　　者：林忠琨[1] 张闰[1] 葛峥[1] 许景艳[2] 刘娟[1] 郭星[1] 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1206-1211,共6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：PAX5是paired-box(PAX)家族重要转录因子。本研究旨在深入探究PAX5基因在成人急性淋巴细胞白血病(acute lymphocytic leukemia,ALL)中的突变、表达特征及其临床意义。应用反转录聚合酶链式反应(RT-PCR)、基因组PCR、克隆和测序技术等检测101例成人ALL患者PAX5基因片段缺失、PAX5基因外显子(exon)2-10的突变;采用定量PCR方法检测PAX5基因表达特征;并研究PAX5突变和表达与临床特征、实验室指标的相关性及其预后意义。结果显示,本组成人ALL患者PAX5突变率7.9%,均发生于B-ALL;共发现PAX5突变类型9种(缺失突变4种、点突变4种和插入突变1种);PAX5突变组年龄≥50岁患者数显著多于无突变组(62.5%vs 21.5%)(P=0.031);PAX5高表达与低表达组之间的B细胞亚型、初诊血小板计数和免疫表型有显著统计学差异(P<0.05);首次诱导治疗完全缓解率在PAX5高表达组高于低表达组(86.7%vs 62.5%)(P=0.030),6个月总生存率PAX5高表达组高于低表达组(75.0%vs 50.0%)(P=0.034)。结论:PAX5基因在成人B-ALL患者中存在缺失、插入和点突变等多种类型突变和异常表达,并与临床参数相关联,具有重要的临床意义。PAX5 is an important transcription factor of paired-box （PAX） family.The aim of this study was to investigate the mutations and expression of PAX5 and its clinical significance in adult patients with acute lymphoblastic leukemia （ALL）.Reverse transcription polymerase chain reaction （RT-PCR） and genomic PCR were performed to detect the deletions of PAX5 and point mutations of PAX5 exon 2-10 in 101 cases of adult ALL and were confirmed by cloning and sequencing.In addition,quantitative PCR （qPCR） was performed to evaluate the expression of PAX5.Furthermore,the correlations of mutations and expression of PAX5 with clinical parameters were analyzed,and the prognostic significance was evaluated as well.The results showed that PAX5 mutations were observed in 8 of 101 （7.9%） patients with B-ALL.A total of 9 types of mutations were detected,including 4 types of deletions,4 types of point mutations and 1 insertion mutation; percentage of patients with age ≥50 years was higher in PAX5 mutation group than in wide-type group（62.5% vs 21.5%,P =0.031）.The statistical differences were observed in B-cell subtype,initial platelet count and immunophenotypes between high and low expression of PAX5 （P 〈 0.05）.In addition,patients with high expression of PAX5 had higher first complete remission rate （86.7% vs 62.5%,P =0.030） and 6-month overall survival rate （75.0% vs 50.0%,P =0.034） compared with patients with low expression of PAX5.It is concluded that deletion/insertion/point mutations and aberrant expression of PAX5 can be observed in adult patients with B-ALL.Mutations and aberrant expression of PAX5 correlated with clinical parameters and have important clinical significance.

关 键 词：PAX5 急性淋巴细胞白血病 成人 

分 类 号：R733.71[医药卫生—肿瘤]