Journal of Shandong University (Health Sciences) ›› 2021, Vol. 59 ›› Issue (11): 35-40.doi: 10.6040/j.issn.1671-7554.0.2021.0791

Previous Articles     Next Articles

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

PDF (PC)

406

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

CLC Number: 

  • R733.7
[1] 中华医学会血液学分会, 中国抗癌协会血液肿瘤专业委员会. 中国慢性淋巴细胞白血病/小淋巴细胞淋巴瘤的诊断与治疗指南(2015年版)[J]. 中华血液学杂志, 2015, 36(10): 809-813.
[2] 中华医学会血液学分会白血病淋巴瘤学组, 中国抗癌协会血液肿瘤专业委员会中国慢性淋巴细胞白血病工作组. 中国慢性淋巴细胞白血病/小淋巴细胞淋巴瘤的诊断与治疗指南(2018年版)[J]. 中华血液学杂志, 2018, 39(5): 353-358.
[3] Yun XY, Zhang Y, Wang X. Recent progress of prognostic biomarkers and risk scoring systems in chronic lymphocytic leukemia [J]. Biomark Res, 2020, 8: 40. doi: 10.1186/s40364-020-00222-3. eCollection 2020.
[4] Yang S, Varghese AM, Sood N, et al. Ethnic and geographic diversity of chronic lymphocytic leukaemia [J]. Leukemia, 2021, 35(2): 433-439.
[5] Yang S, Gale RP, Shi H, et al. Is there an epidemic of chronic lymphocytic leukemia(CLL)in China [J]. Leuk Res, 2018, 73:16-20. doi: 10.1016/j.leukres.2018.08.011.
[6] Pérez-Carretero C, González-Gascón-Y-Marín I, Rodríguez-Vicente AE, et al. The evolving landscape of chronic lymphocytic leukemia on diagnosis, prognosis and treatment [J]. Diagnostics(Basel), 2021, 11(5): 853. doi: 10.3390/diagnostics11050853.
[7] Suzuki R. Molecular pathogenesis and treatment of chronic lymphocytic leukemia [J]. Rinsho Ketsueki,2021, 62(8):1085-1093.
[8] Delgado J, Nadeu F, Colomer D, et al. Chronic lymphocytic leukemia: from molecular pathogenesis to novel therapeutic strategies [J]. Haematologica, 2020, 105(9): 2205-2217. doi: 10.3324/haematol.2019.236000.
[9] 荆源, 林樉, 王芳婷, 等. 荧光原位杂交技术检测43例慢性淋巴细胞白血病患者基因异常[J]. 中国实验血液学杂志, 2018, 26(4): 1038-1043.
[10] 张海英, 杨艳丽, 赵强, 等. 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[J]. 中国实验血液学杂志, 2020, 28(5): 1474-1479.
[11] Baliakas P, Jeromin S, Iskas M, et al. Cytogenetic complexity in chronic lymphocytic leukemia: definitions, associations, and clinical impact [J]. Blood, 2019, 133(11): 1205-1216.
[12] Leeksma AC, Baliakas P, Moysiadis T, et al. Genomic arrays identify high-risk chronic lymphocytic leukemia with genomic complexity: a multicenter study [J]. Haematologica, 2021, 106(1): 87-97.
[13] Tari K, Shamsi Z, Reza Ghafari H, et al. The role of the genetic abnormalities, epigenetic and microRNA in the prognosis of chronic lymphocytic leukemia [J]. Exp Oncol, 2018, 40(4): 261-267.
[14] Stefaniuk P, Onyszczuk J, Szymczyk A, et al. Therapeutic options for patients with TP53 deficient chronic lymphocytic leukemia: narrative review [J]. Cancer Manag Res, 2021, 13: 1459-1476. doi: 10.2147/CMAR.S283903.
[15] Yuan YY, Zhu HY, Wu JZ, et al. The percentage of cells with 17p deletion and the size of 17p deletion subclones show prognostic significance in chronic lymphocytic leukemia [J]. Genes Chromosomes Cancer, 2019, 58(1): 43-51.
[16] 王婷玉, 易树华, 王轶, 等. 氟达拉滨和环磷酰胺联合利妥昔单抗(FCR方案)一线治疗慢性淋巴细胞白血病43例临床分析[J]. 中华血液学杂志, 2021, 42(7): 543-548.
[17] Chauzeix J, Pastoret C, Donaty L, et al. A reduced panel of eight genes(ATM, SF3B1, NOTCH1, BIRC3, XPO1, MYD88, TNFAIP3, and TP53)as an estimator of the tumor mutational burden in chronic lymphocytic leukemia [J]. Int J Lab Hematol, 2021, 43(4): 683-692.
[18] Zou YX, Tang HN, Zhang J, et al. Low prevalence and independent prognostic role of del(11q)in Chinese patients with chronic lymphocytic leukemia [J]. Transl Oncol, 2021, 14(10): 101176. doi: 10.1016/j.tranon.2021.101176.
[19] Aitken MJL, Lee HJ, Post SM, et al. Emerging treatment options for patients with p53-pathway-deficient CLL [J]. Ther Adv Hematol, 2019, 10: 2040620719891356. doi: 10.1177/2040620719891356.
[20] Bagacean C, Tempescul A, Ternant D, et al. 17p deletion strongly influences rituximab elimination in chronic lymphocytic leukemia [J]. J Immunother Cancer, 2019, 7(1):22. doi: 10.1186/s40425-019-0509-0.
[21] Horna P, Pearce KE, Ketterling RP, et al. Recurrent chromosomal abnormalities in tissues involved by chronic lymphocytic leukemia/small lymphocytic lymphoma [J]. Am J Clin Pathol, 2021, aqab128. doi: 10.1093/ajcp/aqab128.
[22] Srinivasan VK, Naseem S, Varma N, et al. Genomic alterations in chronic lymphocytic leukemia and their correlation with clinico-hematological parameters and disease progression [J]. Blood Res, 2020, 55(3): 131-138.
[23] 吕瑞, 李增军, 李姮, 等. FISH检测12号染色体三体阳性慢性淋巴细胞白血病70例临床分析[J]. 中华血液学杂志, 2018, 39(5): 387-391.
[24] Tsagiopoulou M, Chapaprieta V, Duran-Ferrer M, et al. Chronic lymphocytic leukemias with trisomy 12 show a distinct DNA methylation profile linked to altered chromatin activation [J]. Haematologica, 2020, 105(12): 2864-2867.
[25] Wang Y, Achenbach SJ, Rabe KG, et al. Cause of death in patients with newly diagnosed chronic lymphocytic leukemia(CLL)stratified by the CLL-International Prognostic Index [J]. Blood Cancer J, 2021, 11(8): 140. doi: 10.1038/s41408-021-00532-1.
[26] Skórka K, Chojnacki M, Masternak M, et al. The predominant prognostic significance of NOTCH1 Mutation Defined by Emulsion PCR in Chronic Lymphocytic Leukemia [J]. Cancer Manag Res, 2021, 13: 3663-3674. doi: 10.2147/CMAR.S302245. eCollection 2021.
[27] Shetty D, Jain H, Rohil Y, et al. Role of cytogenetic abnormalities detected by fluorescence in situ hybridization as a prognostic marker: Pathogenesis & clinical course in patients with B-chronic lymphocytic leukaemia [J]. Indian J Med Res, 2021, 153(4): 475-483.
[28] Rozovski U, Keating MJ, Estrov Z. Why is the immunoglobulin heavy chain gene mutation status a prognostic Indicator in chronic lymphocytic leukemia [J]. Acta Haematol, 2018, 140(1):51-54.
[29] Bagnara D, Tang C, Brown JR, et al. Post-transformation IGHV-IGHD-IGHJ mutations in chronic lymphocytic leukemia B cells: implications for mutational mechanisms and impact on clinical course [J]. Front Oncol, 2021, 11: 640731. doi: 10.3389/fonc.2021.640731. eCollection 2021.
[30] Basabaeen AA, Abdelgader EA, BaHashwan OS, et al. Combined analysis of ZAP-70 and CD38 expression in sudanese patients with B-cell chronic lymphocytic leukemia [J]. BMC Res Notes, 2019, 12(1): 282. doi: 10.1186/s13104-019-4319-8.
[31] Hu B, Patel KP, Chen HC, et al. Association of gene mutations with time-to-first treatment in 384 treatment-naive chronic lymphocytic leukaemia patients [J]. Br J Haematol, 2019, 187(3): 307-318.
[32] Monti P, Lionetti M, De Luca G, et al. Time to first treatment and P53 dysfunction in chronic lymphocytic leukaemia: results of the O-CLL1 study in early stage patients [J]. Sci Rep, 2020, 10(1):18427. doi: 10.1038/s41598-020-75364-3.
[1] ZHENG Su, CHEN Shuhua, LI Hua, DENG Jie, CHEN Chunhong, WANG Xiaohui, FENG Weixing, HAN Xiaodi, ZHANG Yujia, LI Na, LI Mo, FANG Fang. Correlation between EEG variations and BASED evaluation of the efficacy of ACTH treatment in 54 cases of infantile spasms [J]. Journal of Shandong University (Health Sciences), 2022, 60(9): 91-96.
[2] WANG Lihui, GAO Min, KONG Beihua. Angiosarcoma of the uterus: a report of 2 cases and literature review [J]. Journal of Shandong University (Health Sciences), 2022, 60(9): 108-112.
[3] HE Shiqing, LI Wanwan, DONG Shuqing, MOU Jingyi, LIU Yuying, WEI Siyu, LIU Zhao, ZHANG Jiaxin. Construction of a prognostic risk model of pyroptosis-related genes in breast cancer based on database [J]. Journal of Shandong University (Health Sciences), 2022, 60(8): 34-43.
[4] ZHANG Yufeng, XU Min, XING Xiuli, PANG Shuguang, HU Keqing. Epidemiological characteristics of 689 patients with non-ST-segment elevation myocardial infarction [J]. Journal of Shandong University (Health Sciences), 2022, 60(7): 118-122.
[5] LI Linlin, WANG Kai. Prediction of hepatocellular carcinoma prognostic genes based on bioinformatics [J]. Journal of Shandong University (Health Sciences), 2022, 60(5): 50-58.
[6] SONG Min, ZHOU Yuxia, GAO Lu, LIU Na, WANG Ju, GU Jin, ZHANG Yanping. Prenatal diagnosis for a fetus of mosaic trisomy 6q [J]. Journal of Shandong University (Health Sciences), 2022, 60(5): 109-113.
[7] SUN Zhenguo, TIAN Hui. Optimization of the procedures in minimally invasive esophagectomy: the Qilu practices [J]. Journal of Shandong University (Health Sciences), 2022, 60(11): 33-37.
[8] ZHU Yongcun, ZHAO Xiushi, SUN Nannan, YAO Zhigang, ZHOU Xingchen, MU Kun. Prostate clear cell adenocarcinomas: a report of 3 cases and literature review [J]. Journal of Shandong University (Health Sciences), 2022, 60(11): 102-107.
[9] SHI Xiaohan, LI Huayu, LI Feng. Prognostic factors of elderly patients with glioblastoma treated with Stupp treatment [J]. Journal of Shandong University (Health Sciences), 2022, 60(10): 42-48.
[10] CHEN Liyu, XIAO Juan, LYU Xianzhong, DUAN Baomin, HONG Fanzhen. Risk factors influencing prognosis of lower extremity deep vein thrombosis in pregnant and parturient women [J]. Journal of Shandong University (Health Sciences), 2021, 59(7): 38-42.
[11] TIAN Yaotian, WANG Bao, LI Yeqin, WANG Teng, TIAN Liwen, HAN Bo, WANG Cuiyan. Machine learning models based on interpretive CMR parameters can predict the prognosis of pediatric myocarditis [J]. Journal of Shandong University (Health Sciences), 2021, 59(7): 43-49.
[12] LI Wanwan, ZHOU Wenkai, DONG Shuqing, HE Shiqing, LIU Zhao, ZHANG Jiaxin, LIU Bin. Construct of a risk assessment model of breast cancer immune-related lncRNAs based on the database information [J]. Journal of Shandong University (Health Sciences), 2021, 59(7): 74-84.
[13] CHU Yan, LIU Duanrui, ZHU Wenshuai, FAN Rong, MA Xiaoli, WANG Yunshan, JIA Yanfei. Expressions of DNA methyltransferases in gastric cancer and their clinical significance [J]. Journal of Shandong University (Health Sciences), 2021, 59(7): 1-9.
[14] MI Qi, SHI Shuang, LI Juan, LI Peilong, DU Lutao, WANG Chuanxin. Construction of circRNA-mediated ceRNA network and prognostic assessment model for bladder cancer [J]. Journal of Shandong University (Health Sciences), 2021, 59(6): 94-102.
[15] LI Xiangqing, YIN Xin, ZHAO Xuelian, ZHAO Peiqing. Expression and clinical significance of circulating CD56bright subset of NK cells in patients with Parkinsons disease [J]. Journal of Shandong University (Health Sciences), 2021, 59(2): 34-40.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
[1] SHI Shuang, LI Juan, MI Qi, WANG Yunshan, DU Lutao, WANG Chuanxin. Construction and application of a miRNAs prognostic risk assessment model of gastric cancer[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 47 -52 .
[2] LYU Longfei, LI Lin, LI Shuhai, QI Lei, LU Ming, CHENG Chuanle, TIAN Hui. Application of laparoscopic fine needle catheter jejunostomy in minimally invasive McKeown resection of esophageal cancer[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 77 -81 .
[3] SHAO Haigang, WANG Xuan, WANG Qing. Anatomy of the root canal system of mandibular first premolar in population of Shandong Province[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2014, 52(9): 85 -89 .
[4] LI Wei,LI Dao-wei,YE Qian,GAO Shun-cui,JIANG Shu-juan.

Diagnostic value of transbronchial needle aspiration in paratracheal mediastinal lesions

[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2008, 46(11): 1063 -1065 .
[5] JIANG Bao-dong,MA Xiang-xing,WANG Qing,WANG Qian,FENG Xiao-yuan,LI Ke,YU Fu-hua. Imaging parameters of multislice spiral CT venography in cerebral veins[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2008, 46(11): 1084 -1086 .
[6] WANG Xu-ping,ZHAO Ling,FENG Yu-xin,SHANG Lin-shan,LIU Jin-cheng,. [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2006, 44(6): 564 -567 .
[7] WANG Xue-ping,YANG Hong-ling. [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2007, (2): 213 .
[8] TANG Fang1,2, ZHANG Yingqian3, WANG Zhiqiang4, KANG Dianmin4,
WANG Jiezhen1, XUE Fuzhong1. A 2D minimal spanning tree model of the spatial structures of natural focal disease[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2009, 47(01): 106 -110 .
[9] HUANG Sheng-yun,ZHANG Dong-sheng,ZHANG Shi-zhou,LIU Gui-jun,ZHAO Yue-ran,WANG Lai-cheng,LIU Yi-qing. Construction of recombination expression vector pIRES-CD and pIRES-TK and their expression in ACC-2 cells[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2007, 45(2): 117 -123 .
[10] LI Yu-liang,WANG Yong-zheng,WANG Xiao-hua,ZHANG Fu-jun,ZHU Li-dong,ZHANG Wang-ming,LI Zheng,LI Zhen-jia,ZHANG Kai-xian. I implantation combined with Gemcitabine in the treatment of advanced pancreatic cancer[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2007, 45(4): 393 -396 .
Copyright 2018 © Editorial office of Journal of Shandong University (Health Sciences)
Supported by Beijing Magtech Co.Ltd