荧光原位杂交技术检测慢性淋巴细胞白血病分子遗传学异常  

Fluorescence in Situ Hybridization for Detecting Molecular Cytogenetic Abnormalities of Chronic Lymphocytic Leukemia

作　　者：张海英 杨艳丽 赵强 张京 白海 ZHANG Hai-Ying;YANG Yan-Li;ZHAO Qiang;ZHANG Jing;BAI Hai(Department of Pathology,The 940th Hospital of Joint Logistic Support of Chinese PLA,Lanzhou 730050,Gansu Province,China;Department of Hematology,The 940th Hospital of Joint Logistic Support of Chinese PLA,Lanzhou 730050,Gansu Province,China)

机构地区：[1]联勤保障部队第九四○医院病理科,甘肃兰州7300550 [2]联勤保障部队第九四○医院血液科,甘肃兰州7300550

出　　处：《中国实验血液学杂志》2020年第5期1474-1479,共6页Journal of Experimental Hematology

摘　　要：目的:探讨荧光原位杂交技术(fluorescence in situ hybridization,FISH)在慢性淋巴细胞白血病(CLL)诊断和预后评估中的价值。方法:采用RB1(13q14.1)、D13S25(13q14.3)、p53(17p13.1)、ATM(11q22.3)及CSP125组探针对93例初诊CLL患者进行检测,同期进行常规染色体核型(conventional cytogenetics,CC)分析。分析FISH检测出的遗传学异常与患者的临床Binet分期、Rai分期及其他检测指标的相关性。结果:93例初诊CLL患者分子遗传学异常检出率为79.6%(74/93),其中13q缺失(13q-)阳性率最高,占45.2%;其次为12号染色体三体(+12)占26.9%、p53缺失(17p-)占19.4%、ATM缺失(11p-)占17.2%。同时伴有2种及2种以上染色体异常患者27例(29.0%),其中13q-伴17p-者8例,13q-伴11q-者5例,13q-伴+12者4例。CC检测结果相比较,FISH检测结果中患者的阳性率非常显著高于CC检测结果(χ^2=32.127,P<0.01)。FISH检测结果与Rai分期没有显著相关性(P>0.05),伴17p-的CLL患者Binet分期更晚(P=0.012)。各分子遗传学异常与患者年龄、外周血淋巴细胞计数绝对值和CD38表达水平之间均无显著相关性(P>0.05)。女性患者13q-的发生率(65.4%)显著高于男性患者(37.3%)(P=0.015);17p-患者IGHV未突变(U-IGHV)的比例显著高于17p-阴性患者(P=0.013);29.0%的患者表达CD38,且与临床分期及U-IGHV呈显著相关(P值分别为0.027及0.006)。结论:FISH技术能够大大地提高CLL患者分子遗传学异常的检出率,是常规细胞遗传学有力的补充,对CLL患者的临床分期及预后判断均有重要的应用价值。Objective:To investigate the value of fluorescence in situ hybridization(FISH)in the diagnosis and prognosis evaluation of patients with chronic lymphocytic leukemia(CLL).Methods:Ninty-three patients with newly diagnosed CLL were tested by five probes including RB1(13 q14.1),D13 S25(13 q14.3),p53(17 p13.1),ATM(11 q22.3)and CSP12,while conventional cytogenetics(CC)was used for karyotype analysis.Then the correlation of the molecular cytogenetic abnormalities with the clinical Binet stages,Rai stages and the other related laboratory examinations was analyzed.Results:The detection rate of chromosome abnormality in 93 patients was 79.6%,out of which detection rate of 13 q(13 q-was the highest and accounted for 45.2%),followed by trisomy 12(+12)26.9%,p53 deletion(17 p-)19.4%and ATM deletion(11 p-)17.2%.There were 27 cases(29.0%)with 2 or more abnormalities,including 13 cases with 13 q-/17 q-,5 with 13 q-/11 q-,and 4 with 13 q-/+12.Compared with CC test results,the positive rate of FISH detection was significantly higher(χ^2=32.127,P<0.01).There was no significant correlation between FISH results and Rai stages(P>0.05),meanwhile 17 p-highly correlated with later stage of the Binet stages(P=0.012).The molecular cytogenetic abnormalities significantly correlated with age,absolute value of peripheral lymphocyte count and CD38 expression level(P>0.05).The incidence of 13 q-in female(65.4%)was statistically significantly higher than that in male(37.3%)(P=0.015).The unmutated IGHV rate of CLL patients with a 17 p-was significantly higher than that in patients without this genetic abnormality(P=0.013).The expression of CD38 was detected among 29.0%of the patients,which significantly correlated with Binet stages(P=0.027)and unmutated IGHV(P=0.006).Conclusion:FISH can greatly increase the detection rate of molecular cytogenetic abnormalities in CLL patients,which,as a powerful supplement to the conventional cytogenetics,can be applied for the clinical staging and prognosis evaluation of CLL patients.

关 键 词：慢性淋巴细胞白血病 荧光原位杂交 染色体核型分析 

分 类 号：R733.7[医药卫生—肿瘤]