急性淋巴细胞白血病的免疫分型和基因的研究  

Study on Immunophenotypes and Gene of Acute Lymphoblastic Leukemia

作　　者：赵雪飞[1] 王洪岩[1] 赵旭[1] 程焕臣 李蔚[1] 刘生伟[1] 邱林[1] 马军[1] ZHAO Xue-Fei;WANG Hong-Yan;ZHAO Xu;CHENG Huan-Chen;LI Wei;LIU Sheng-Wei;QIU Lin;MA Jun(center of Hematology and Oncology,The First Hospital of Harbin,Harbin,150010,Heilongjiang Province,China)

机构地区：[1]哈尔滨市第一医院血液肿瘤研究中心,黑龙江哈尔滨150010

出　　处：《中国实验血液学杂志》2018年第4期947-952,共6页Journal of Experimental Hematology

摘　　要：目的:回顾性分析30例急性淋巴细胞白血病(ALL)患者的免疫分型,融合基因及基因突变的分子生物学检测结果,并探讨其与临床治疗效果及预后的关系。方法:选取哈尔滨市第一医院血液肿瘤研究中心2015年8月到2016年6月经过骨髓细胞形态学、免疫表型、细胞遗传学、分子生物学等检查确诊的ALL患者30例,按照FAB标准分类,27例为B系ALL,3例为T系ALL。分析ALL患者白血病细胞膜表面及胞浆内分化抗原,并且对所有患者都进行43种融合基因定性筛查(BCR-ABL,AML1-ETO,PML-RARα等)和ALL基因突变(IKZF1,TP53,PAX5,JAK1,JAK2,CRLF2,PHF6,NOTCH1,FBXW7,PTEN)的二代测序(NGS)检测。结果:30例ALL患者中男性14例,女性16例,年龄2-74岁,中位年龄11.5岁。30例ALL中B-ALL发病率(90.00%)明显高于T-ALL(10.00%)。27例B-ALL患者主要表达CD19、CD22、CD10和CD34等。CD19和CD22是B-ALL最具有诊断价值的抗原;3例T-ALL主要表达cCD3、CD7、CD10和cTDT等,CD7和cCD3是T-ALL最具有诊断价值的抗原。30例ALL患者的43种融合基因定性筛查发现,BCR-ABL、TEL-AML1、E2A-PBX1、MLL-AF6、MLL-AF4和SIL-TAL融合基因阳性各1例,ALL相关基因突变的NGS检测结果表明,3例B-ALL患者发生TP53突变,1例B-ALL患者发生TET2 I1762V突变;3例患者(2例T-ALL,1例B-ALL)发现NOTCH1基因突变。1个疗程后成人B-ALL的治疗效果(28.57%)明显差于儿童B-ALL(95.00%),截止至2017年7月10日儿童B-ALL的生存率明显优于成人B-ALL,其差异都具有显著性意义。结论:白血病免疫分型技术及分子生物学检测技术在白血病的诊断、治疗方案的选择及疗效评价方面具有重要指导作用,是骨髓细胞形态学诊断的补充。Objective： To retrospectively analyze the immunophenotyping, fusion gene and gene mutation of 30 acute lymphoblastic leukemia（ALL） cases and to investigate the relationship between the analysis results and the clinical therapeutic effect and prognosis. Methods： Thirty All phtients were collected from the First Hospital of Harbin, Institute of Hematology and Oncology Department of Pediatrics from August 2015 to June 2016. According to the classification of FAB standard, 27 cases were B system ALL, 3 cases were T system ALL. All patients were diagnosed by bone marrow cell morphology, immunophenotype, cytogenetics and molecular biology detetions, the differentiation antigens on membrane surface and in cytoplasm of ALL cells, and 43 kinds of fusion gene qualitative screening（BCR-ABL, AML1-ETO, PML-RARα and so on） were qualitative screened and ALL gene mutations（IKZF1, TP53, PAX5, JAK1, JAK2,CRLF2, PHF6, NOTCH1, FBXW7, PTEN）were detected by next generation sequencing（NGS）. Results：（1） Among 30 ALL patients, the incidence of B-ALL（90.00%） was higher than that of T-ALL（10.00%）.（2） 27 cases of B-ALL expressed CD19, CD22, CD10, CD34 and so on. CD19 and CD22 were the most diagnostic antigens of B-ALL.（3） 3 cases of T-ALL mainly expressed cCD3, CD7, CD10, cTDT and so on; cCD3 and CD7 were the most diagnostic antigens of T-ALL.（4）The quantitative screening of 30 cases of ALL 43 fusion genes found BCR-ABL,TEL-AML1 and E2 A-PBX1, MLL-AF6,MLL-AF4, and SIL-TAL1 fusion gene was positive in 1 case each; NGS detection of gane mutations associated with ALL showed that： 3 cases of B-ALL found that TP53 mutation occured 3 casas of B-ALL, TET2 I1762 V mutations in 1 cases,3 patients（2 cases of T-ALL, 1 cases of B-ALL） showed NOTCH1 gene mutation. After a cycle of treatment, the efficacy of adult B-ALL treatment（28.57%） was significantly lower than that of child B-ALL（95.00%）, and the survival rate of child B-ALL was significantly better than that of adult B-ALL until July 10,

关 键 词：急性淋巴细胞白血病 白血病免疫分型 融合基因定性筛查 基因突变的二代测序检测 

分 类 号：R733.71[医药卫生—肿瘤]