慢性髓性白血病患者BCR-ABL融合基因的规范化检测及临床应用

doi:10.3969/j.issn.1004-583X.2021.10.004

临床荟萃 ›› 2021, Vol. 36 ›› Issue (10): 884-888.doi: 10.3969/j.issn.1004-583X.2021.10.004

• 专题:血液病诊疗关键技术转化与推广 • 上一篇下一篇

慢性髓性白血病患者BCR-ABL融合基因的规范化检测及临床应用

秦亚溱()

北京大学人民医院,北京大学血液病研究所,国家血液系统疾病临床医学研究中心,北京 100044

收稿日期:2021-07-15 出版日期:2021-10-20 发布日期:2021-11-10
通讯作者: 秦亚溱 E-mail:qin2000@aliyun.com
作者简介:秦亚溱,研究员,硕士生导师。中华医学会血液学分会第九届/第十届/第十一届实验诊断学组委员,中国生物工程学会第一届细胞分析专业委员会委员。研究方向:恶性血液病转化研究及分子诊断。主持4项国家自然科学基金及1项北京市基金。以第一或通讯作者(含共同)发表SCI论文30余篇,中文论文30余篇。主持3项全国血液分子检测室间比对项目。执笔(含参与)3项血液病分子诊断中国专家共识/指南。获得首都转化医学创新大赛优秀项目奖。

Standardized detection of BCR-ABL mRNA and clinical application in patients with chronic myeloid leukemia

Qin Yazhen()

Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing 100044, China

Received:2021-07-15 Online:2021-10-20 Published:2021-11-10
Contact: Qin Yazhen E-mail:qin2000@aliyun.com

摘要/Abstract

摘要：

BCR-ABL融合基因(mRNA)是慢性髓性白血病(CML)的分子标志,靶向BCR-ABL的酪氨酸激酶抑制剂(TKIs)是当前CML治疗的基本药物。BCR-ABL mRNA水平是TKI疗效评估的重要指标,ABL酪氨酸激酶区突变提示耐药机制、指导随后TKIs的选择等治疗策略。规范化的BCR-ABL检测是精准指导临床治疗的前提,是CML患者获得最佳疗效的保证。规范化体现在样本类型、检测内容、实验室检测方案、报告方式等方面,本文结合新近文献探讨了CML患者BCR-ABL定量和突变的规范化检测及临床应用。

关键词: 白血病,髓样,慢性, 融合蛋白质类,BCR-ABL, 受体蛋白质酪氨酸激酶类, 规范化

Abstract:

BCR-ABL mRNA is the molecular marker of chronic myeloid leukemia(CML), and tyrosine kinase inhibitors(TKIs) targeting BCR-ABL mRNA has become the basic drug for CML. BCR-ABL mRNA level is the important indicator for evaluation of TKI efficacy. The mutation in ABL tyrosine kinase domain suggests mechanism of TKI resistance, which could guide the treatment strategy such as the selection of next TKIs. Standardized detection of BCR-ABLmRNA is essential for precisely guiding treatment and the guarantee for CML patients to achieve the best curative effects. Standardization is involved in sample type, testing content, laboratory protocol and report ways. This paper explored the standardized detection of quantification and mutation of BCR-ABL and clinical application in CML patients based on recent literature.

Key words: leukemia,myeloid,chronic, fusion proteins,BCR-ABL, receptor protein-tyrosine kinases, standardization

中图分类号:

R733.72

秦亚溱. 慢性髓性白血病患者BCR-ABL融合基因的规范化检测及临床应用[J]. 临床荟萃, 2021, 36(10): 884-888.

Qin Yazhen. Standardized detection of BCR-ABL mRNA and clinical application in patients with chronic myeloid leukemia[J]. Clinical Focus, 2021, 36(10): 884-888.

导出引用管理器 EndNote|Ris|BibTeX

链接本文: https://huicui.hebmu.edu.cn/CN/10.3969/j.issn.1004-583X.2021.10.004

https://huicui.hebmu.edu.cn/CN/Y2021/V36/I10/884

图/表 2

参考文献 22

[1]	Rowley JD. A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining[J]. Nature, 1973,243(5405):290-293. doi: 10.1038/243290a0 URL
[2]	Bartram CR, de Klein A, Hagemeijer A, et al. Translocation of c-abl oncogene correlates with the presence of a Philadelphia chromosome in chronic myelocytic leukaemia[J]. Nature, 1983,306(5940):277-280. doi: 10.1038/306277a0 URL
[3]	Björkholm M, Ohm L, Eloranta S, et al. Success story of targeted therapy in chronic myeloid leukemia: a population-based study of patients diagnosed in Sweden from 1973 to 2008[J]. J Clin Oncol, 2011,29(18):2514-2520. doi: 10.1200/JCO.2011.34.7146 pmid: 21576640
[4]	Kantarjian H, O'Brien S, Jabbour E, et al. Improved survival in chronic myeloid leukemia since the introduction of imatinib therapy: a single-institution historical experience[J]. Blood, 2012,119(9):1981-1987. doi: 10.1182/blood-2011-08-358135 pmid: 22228624
[5]	Daley GQ, van Etten RA, Baltimore D. Induction of chronic myelogenous leukemia in mice by the P210bcr/abl gene of the Philadelphia chromosome[J]. Science, 1990,247(4944):824-830. pmid: 2406902
[6]	Melo JV. BCR-ABL gene variants[J]. Baillieres Clin Haematol, 1997,10(2):203-222. doi: 10.1016/S0950-3536(97)80003-0 URL
[7]	Qin YZ, Jiang Q, Jiang H, et al. Prevalence and outcomes of uncommon BCR-ABL1 fusion transcripts in patients with chronic myeloid leukaemia: data from a single centre[J]. Br J Haematol, 2018,182(5):693-700. doi: 10.1111/bjh.15453 URL
[8]	Qin YZ, Huang XJ. Molecular detection of BCR-ABL in chronic myeloid leukemia[J]. Methods Mol Biol, 2016,1465:1-15.
[9]	秦亚溱, 主鸿鹄, 黄晓军. 慢性髓性白血病分子监测手册[M]. 北京: 人民卫生出版社, 2013.
[10]	Hochhaus A, Baccarani M, Silver RT, et al. European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia[J]. Leukemia, 2020,34(4):966-984. doi: 10.1038/s41375-020-0776-2 pmid: 32127639
[11]	National Comprehensive Cancer Network clinical practice guidelines in oncology (NCCN Guidelines): Chronic myeloid leukemia[S]. Version 3. 2021.
[12]	中华医学会血液学分会. 慢性髓性白血病中国诊断与治疗指南(2020年版)[J]. 中华血液学杂志, 2020,41(5):353-364.
[13]	Hughes TP, Ross DM. Moving treatment-free remission into mainstream clinical practice in CML[J]. Blood, 2016,128(1):17-23.
[14]	von Bubnoff N, Schneller F, Peschel C, et al. BCR-ABL gene mutations in relation to clinical resistance of Philadelphia-chromosome-positive leukaemia to STI571: a prospective study[J]. Lancet, 2002,359(9305):487-491. doi: 10.1016/S0140-6736(02)07679-1 URL
[15]	Hughes TP, Deininger M, Hochhaus A, et al. Monitoring CML patients responding to treatment with tyrosine kinase inhibitors: review and recommendations for harmonizing current methodology for detecting BCR-ABL transcripts and kinase domain mutations and for expressing results[J]. Blood, 2006,108(1):28-37.
[16]	Branford S, Fletcher L, Cross NC, et al. Desirable performance characteristics for BCR-ABL measurement on an international reporting scale to allow consistent interpretation of individual patient response and comparison of response rates between clinical trials[J]. Blood, 2008,112(8):3330-3338. doi: 10.1182/blood-2008-04-150680 pmid: 18684859
[17]	Müller MC, Cross NC, Erben P, et al. Harmonization of molecular monitoring of CML therapy in Europe[J]. Leukemia, 2009,23(11):1957-1963. doi: 10.1038/leu.2009.168 pmid: 19710700
[18]	秦亚溱, 林振兴, 岑建农, 等. 用于转换国际标准的BCR-ABL (P210)转录本水平的转换系数多中心确认研究[J]. 中华血液学杂志, 2014,35(2):134-137.
[19]	秦亚溱, 马道新, 王云贵, 等. 转换国际标准化的 BCR-ABL(P210)转录本水平的转换系数多中心再确认研究[J]. 中华血液学杂志, 2015,36(10):814-817.
[20]	中华医学会血液学分会实验诊断学组, 中国医师协会中国慢性髓性白血病联盟. BCR-ABL酪氨酸激酶区突变检测实验室规范中国专家共识(2015 年版)[J]. 中华血液学杂志, 2015,36(11):899-901.
[21]	Branford S, Hughes TP, Rudzki Z. Monitoring chronic myeloid leukaemia therapy by real-time quantitative PCR in blood is a reliable alternative to bone marrow cytogenetics[J]. Br J Haematol, 1999,107(3):587-599. doi: 10.1046/j.1365-2141.1999.01749.x URL
[22]	Jiang Q, Zhao XY, Qin YZ, et al. The differences and correlations of BCR-ABL transcripts between peripheral blood and bone marrow assays are associated with the molecular responses in the bone marrow for chronic myelogenous leukemia[J]. Am J Hematol, 2012,87(12):1065-1069. doi: 10.1002/ajh.23321 pmid: 22965919

治疗时间	最佳 (%)	警告 (%)	失败 (%)
3个月	≤10	>10	如果在1~3个月确认 >10
6个月	≤1	>1~10	>10
12个月	≤0.1	>0.1~1	>1
之后任何时间	≤0.1	>0.1~1, 丧失≤0.1	>1,耐药型ABL突变,高危附加染色体异常

治疗时间	最佳 (%)	警告 (%)	失败 (%)
3个月	≤10	>10	如果在1~3个月确认 >10
6个月	≤1	>1~10	>10
12个月	≤0.1	>0.1~1	>1
之后任何时间	≤0.1	>0.1~1, 丧失≤0.1	>1,耐药型ABL突变,高危附加染色体异常

反应类型	定义
MMR	BCR-ABL^IS≤0.1%
MR4.0	BCR-ABL^IS≤0.01%
	或BCR-ABL^IS=0同时ABL copies≥10 000
MR4.5	BCR-ABL^IS≤0.0032%
	或BCR-ABL^IS=0同时ABL copies≥32 000
MR5.0	BCR-ABL^IS≤0.001%
	或BCR-ABL^IS=0同时ABL copies≥100 000

反应类型	定义
MMR	BCR-ABL^IS≤0.1%
MR4.0	BCR-ABL^IS≤0.01%
	或BCR-ABL^IS=0同时ABL copies≥10 000
MR4.5	BCR-ABL^IS≤0.0032%
	或BCR-ABL^IS=0同时ABL copies≥32 000
MR5.0	BCR-ABL^IS≤0.001%
	或BCR-ABL^IS=0同时ABL copies≥100 000

慢性髓性白血病患者BCR-ABL融合基因的规范化检测及临床应用

Standardized detection of BCR-ABL mRNA and clinical application in patients with chronic myeloid leukemia

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

图/表 2

参考文献 22

相关文章 7

编辑推荐

Metrics

本文评价

[1]	付海霞. 原发免疫性血小板减少症的规范化诊治[J]. 临床荟萃, 2021, 36(10): 896-900.
[2]	刘巧雪, 魏辉. 急性髓细胞白血病的规范化治疗[J]. 临床荟萃, 2021, 36(10): 880-883.
[3]	雷玲彦，郭惠芳. 脊柱关节炎规范化诊治进展[J]. 临床荟萃, 2019, 34(4): 299-305.
[4]	任金海;郭晓楠;林凤茹. 2013年慢性粒细胞白血病和其他慢性骨髓增殖性肿瘤的研究进展[J]. 临床荟萃, 2014, 29(3): 270-274.
[5]	刘耀;张曦. 套细胞淋巴瘤的治疗现状及进展[J]. 临床荟萃, 2014, 29(10): 1140-1146.
[6]	许卓文;杜媛鲲. 医学论文中插图的正确表达和编辑加工[J]. 临床荟萃, 2013, 28(9): 1079-1080.
[7]	胡大一;赵明中. 坚持循证医学原则,重视急性冠状动脉综合征的规范化治疗[J]. 临床荟萃, 2004, 19(3): 121-123.