IKZF1基因在BCR/ABL融合基因阳性急性淋巴细胞白血病中的表达及机制探讨  

The expression and mechanism of IKZF1 gene in BCR/ABL fusion gene positive acute lymphoblastic leukemia

作　　者：刘锋[1] 温静 李光[1] 戴进前[1] 杜明珠[1] 宋艳萍[1] LIU Feng;WEN Jing;LI Guang;DAI Jinqian;DU Mingzhu;SONG Yanping(Institute of Hematology of Xi'an,Xi'an Central Hospital,Shaanxi Xi'an 710004,China)

机构地区：[1]西安市中心医院西安市血液病研究所,陕西西安710004

出　　处：《现代肿瘤医学》2022年第4期603-607,共5页Journal of Modern Oncology

基　　金：陕西省西安市科技计划项目[编号:201805095YX3SF29(3)]。

摘　　要：目的:探讨IKZF1基因在急性淋巴细胞白血病中的表达特点及可能机制,进一步明确急性淋巴细胞白血病的发病机理。方法:收取80例急性淋巴细胞白血病患者的外周血标本,其中21例BCR/ABL融合基因阳性,均为B细胞急性淋巴细胞白血病。RT-PCR技术检测IKZF1基因、RAG1基因及RAG2基因的表达;提取细胞DNA,PCR技术检测IKZF1基因的缺失突变;二代测序了解IKZF1基因断裂点区域的碱基序列。结果:RT-PCR结果显示80例急性淋巴细胞白血病中19例表达IK6亚型,其中17例为BCR/ABL融合基因阳性B细胞急性淋巴细胞白血病,2例为BCR/ABL融合基因阴性B细胞急性淋巴细胞白血病。即IK6亚型的表达主要在B细胞急性淋巴细胞白血病中,且主要与BCR/ABL融合基因有关。PCR实验证实了BCR/ABL融合基因阳性B细胞急性淋巴细胞白血病中IKZF1基因发生了缺失突变。二代测序发现IK6亚型由IKZF1基因2号内含子和6号内含子异常断裂后拼接形成,断裂点处存在重组激活基因蛋白能靶向作用的cRSS序列。结论:IK6亚型的表达主要在B细胞急性淋巴细胞白血病中。IK6亚型的表达在急性淋巴细胞白血病中与BCR/ABL融合基因有关。IK6亚型的表达在BCR/ABL融合基因阳性急性淋巴细胞白血病中与重组激活基因蛋白靶向作用导致IKZF1基因2号和6号内含子断裂可能相关。Objective:To explore the expression characteristics and possible mechanism of IKZF1 gene in acute lymphoblastic leukemia,and to further clarify the pathogenesis of acute lymphoblastic leukemia.Methods:Peripheral blood samples of 80 patients with acute lymphoblastic leukemia were collected,of which 21 patients were positive for BCR/ABL fusion gene,all of which were B-cell acute lymphoblastic leukemia.RT-PCR technology detected the expression of IKZF1 gene,RAG1 gene and RAG2 gene.Cell DNA was extracted.PCR technology detected the deletion mutation of IKZF1 gene.Second-generation sequencing was used to understand the base sequence of the breakpoint region of IKZF1 gene.Results:RT-PCR result showed 19 patients of 80 patients with acute lymphoblastic leukemias expressed IK6 subtype.Among these 19 cases,17 of whom were BCR/ABL fusion gene-positive B-cell acute lymphoblastic leukemia,and 2 of whom were BCR/ABL fusion gene-negative B-cell acute lymphoblastic leukemia.That was,the expression of IK6 subtype was mainly in B-cell acute lymphoblastic leukemia,and was mainly related to the BCR/ABL fusion gene.PCR experiment confirmed that the deletion mutation of IKZF1 gene in B-cell acute lymphoblastic leukemia with positive BCR/ABL fusion gene.Second-generation sequencing revealed that the IK6 subtype was formed by abnormally splitting and splicing between intron 2 and intron 6 of IKZF1 gene,and there was a cRSS sequence that can be targeted by recombination activating gene protein at the break point.Conclusion:The expression of IK6 subtype is mainly in B-cell acute lymphoblastic leukemia.The expression of IK6 subtype is related to the BCR/ABL fusion gene in acute lymphoblastic leukemia.The expression of IK6 subtype in BCR/ABL fusion gene-positive acute lymphoblastic leukemia may be related to the rupture of introns 2 and 6 of IKZF1 gene caused by the targeting of recombination activating gene protein.

关 键 词：急性淋巴细胞白血病 BCR/ABL IKZF1 IK6 cRSS 重组激活基因蛋白 

分 类 号：R733.71[医药卫生—肿瘤]