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山东大学学报 (医学版) ›› 2021, Vol. 59 ›› Issue (11): 35-40.doi: 10.6040/j.issn.1671-7554.0.2021.0791

• 临床医学 • 上一篇    下一篇

荧光原位杂交对197例慢性淋巴细胞白血病的诊断

曾睿1,2,胡欣婷1,2,云晓雅1,2,田筝1,2,李青1,刘杰1,张娅1,2,王欣1,2   

  1. 1. 山东大学附属省立医院血液科, 山东 济南 250021;2. 山东第一医科大学附属省立医院血液科, 山东 济南 250021
  • 发布日期:2021-11-11
  • 通讯作者: 王欣. E-mail:xinw007@126.com张娅. E-mail:maryzhangya@gmail.com

Fluorescence in situ hybridization in the diagnosis of 197 cases of chronic lymphocytic leukemia

ZENG Rui1,2, HU Xinting1,2, YUN Xiaoya1,2, TIAN Zheng1,2, LI Qing1, LIU Jie1, ZHANG Ya1,2, WANG Xin1,2   

  1. 1. Department of Hematology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, Shandong, China;
    2. Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong, China
  • Published:2021-11-11

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摘要： 目的 探讨荧光原位杂交技术(FISH)在慢性淋巴细胞白血病(CLL)诊断与预后评估中的应用,指导CLL患者的精准个体化诊疗。 方法 对2014年1月至2021年1月收治的197例CLL患者采用 RB1(13q14.1)、D13S25(13q14.3)、p53(17p13.1)、ATM(11q22.3)及CSP12(+12)5组基因探针进行FISH检测,对其中62例进行染色体核型分析、75例进行免疫球蛋白重链可变区(IGHV)突变状态检测,分析FISH检测细胞遗传学改变在CLL中的临床意义。 结果 197例初诊CLL患者分子遗传学标志物异常总检出率为56.4%(111/197),其中D13S25(13q14.3)占63.1%(70/111)、RB1(13q14.1)占43.2%(48/111)、p53(17p13.1)占29.7%(33/111)、ATM(11q22.3)占22.5%(25/111)、CSP12(+12)占13.5%(15/111)。同时伴有2种染色体异常患者占34.2%(38/111),其中RB1与D13S25双阳性患者占25.2%(28/111)。同时伴有3种及3种以上染色体异常患者占16.2%(18/111)。相比于CLL患者的染色体核型分析结果,FISH 检测阳性率相对较高(P<0.001)。另外,FISH检测结果与CLL国际预后指数(CLL-IPI)有关。FISH检测阳性CLL患者中CLL-IPI评分为高危/极高危的比例高于FISH检测阴性患者(P=0.009)。FISH-p53阳性CLL患者的CLL-IPI评分均为高危/极高危(P<0.001)。FISH阳性患者中IGHV基因突变者占78%,未突变者占22%。 结论 FISH技术是一种敏感的CLL分子遗传学检测手段,对CLL患者的预后评估和治疗均有重要的指导意义。

关键词: 慢性淋巴细胞白血病, 荧光原位杂交, 细胞遗传学, 预后, 染色体核型分析

Abstract: Objective To explore the application of fluorescence in situ hybridization(FISH)in the diagnosis and prognosis assessment of chronic lymphocytic leukemia(CLL). Methods The 197 CLL patients treated during Jan. 2014 and Jan. 2021 received molecular genetic tests with RB1(13q14.1), D13S25(13q14.3), P53(17p13.1), ATM(11q22.3)and CSP12(+12), 62 of whom underwent karyotype analysis and 75 immunoglobulin heavy chain variable region(IGHV)mutation status detection. Results The total detection rate of abnormal molecular genetic markers was 56.4%(111/197). D13S25(13q14.3)accounted for 63.1%(70/111), followed by RB1(13q14.1)43.2%(48/111), p53(17p13.1)29.7%(33/111), ATM(11q22.3)22.5%(25/111), and CSP12(+12)13.5%(15/111). Patients with 2 chromosomal abnormalities accounted for 34.2%(38/111), among whom RB1 and D13S25 double-positive patients accounted for 25.2%(28/111). Patients with 3 or more chromosomal abnormalities accounted for 16.2%(18/111). The positive rate of FISH was significantly higher than that of conventional cytogenetics(P<0.001). The results of FISH test were correlated with the International Prognostic Index for Chronic Lymphocytic Leukemia(CLL-IPI). The proportion of high-risk and very high-risk patients with positive FISH test results was larger than that with negative FISH test results(P=0.009). The CLL-IPI scores of FISH-P53 positive patients were high or very high(P<0.001). Among FISH positive patients, 78% were IGHV mutated and 22% were IGHV unmated. Conclusion FISH is a critical molecular genetic detection method with higher sensitivity than chromosome karyotype analysis, which can provide rational guidance for the prognosis evaluation and treatment of CLL patients.

Key words: Chronic lymphocytic leukemia, Fluorescence in situ hybridization, Cytogenetics, Prognosis, Chromosome karyotype

中图分类号: 

  • R733.7
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