儿童急性白血病T细胞受体δ、γ基因重排连接区序列的动态分析  

Dynamic analysis of junctional sequences of T cell receptor(TCR) δ and γ gene rearrangement in childhood with acute lymphoblastic leukemia

作　　者：卢洁[1] 谷仁凯[1] 雷珂[1] 王学淳[2] 孙立荣[1] 庞秀英[1] 李学荣[1] 董增义[1] 

机构地区：[1]青岛大学医学院附属医院儿科研究所,266003 [2]青岛市立医院

出　　处：《中华血液学杂志》2000年第6期301-304,共4页Chinese Journal of Hematology

基　　金：山东省自然科学基金资助项目!(Y97C170 5 3 );山东省"九五"医药科技攻关资助项目!(鲁卫科教字 [1997]第九号 )

摘　　要：目的　探讨儿童急性淋巴细胞白血病 (ALL)患者在初诊、完全缓解 (CR)及复发不同时期的T细胞受体 (TCR)δV D、γV J基因重排连接区序列的差异及其意义。方法　采用T 载体分子克隆测序、限制性酶切及聚合酶链反应等技术 ,对 34份ALL患者标本进行TCRδ、γ连接区序列动态分析。结果　 34份ALL患者标本的TCRδ、γ基因重排序列在初诊、CR及复发不同转归时期显示有差异性和规律性。TCRδV D重排序列分析显示 ,2 4份ALL患者标本中 ,10份初诊患者Vδ2、Dδ3序列较完整 ,其中 7份伴有Dδ3的九碱基序列区T→C突变。 11份CR期患者有明显Vδ2的 3′端、Dδ3的 5′端及七碱基序列重排序列缺失 ,Dδ3九碱基序列区T→C突变消失。初诊与CR期ALL患者Vδ2或Dδ3重排序列缺失率及Dδ3九碱基序列区T→C突变率比较 ,差异均有极显著性意义 (精确概率计算 ,P均 =0 .0 0 1)。 3份复发患者标本均保留Dδ3的 5′端重排序列完整。 10份TCRγV J序列分析结果规律性与δ相似。结论　ALL的TCRδV D、TCRγV J基因重排序列的改变与ALL的发生、疗效及转归有着密切的内在联系。Objective To explore the junctional sequence difference of T cell receptor δ and γ gene rearrangement in childhood acute lymphoblastic leukemia (ALL) at diagnosis, complete remission (CR) and relapse. Methods By using the T vector molecular cloning and sequencing and polymerase chain reaction, the junctional sequences of TCRδV D and TCRγV J were dynamically analyzed in 34 bone marrow samples of ALL. Results The junctional sequence of TCR δ、γ gene showed significant difference and regularity before and after remission and during relapsed periods. The sequence of TCRδV D were analyzed in 24 samples from ALL. Among them, the intact Vδ2 and 5′Dδ3 sequences were observed in 10 samples at diagnosis, of which 7 samples had T→C mutation in Dδ3 nonamer sequence. The deletions of rearranged Vδ2, 5′Dδ3 and Dδ3 haptamer sequences were found in 11 complete remission (CR) samples with ALL, but none had T→C mutation in Dδ3 nonamer sequence. The deletion rate of Vδ2 or Dδ3 sequences and the T→C mutation in Dδ3 nonamer sequence were extremely differed between samples at diagnosis and in remission (calculate exact probabilities P=0.001). The junctional rearrangement sequence of 5′Dδ3 sequences tended to remain intact in 3 relapsed samples. The findings of TCRγV J sequences were similar to that of TCRδV D in 10 ALL patients. Conclusion The difference of TCRδV D and TCRγV J junctional sequences were related to the development, therapeutic effectiveness and outcome in ALL.

关 键 词：急性白血病 T细胞受体 分子克隆 基因重排 

分 类 号：R733.71[医药卫生—肿瘤]