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中国生物工程杂志

CHINA BIOTECHNOLOGY
中国生物工程杂志  2019, Vol. 39 Issue (9): 11-18    DOI: 10.13523/j.cb.20190902
研究报告     
成人t(8;21)急性髓系白血病患者初诊Ki-67的表达特征及预后意义 *
刀凤亭,杨璐,王亚哲,常艳,袁晓英,李玲娣,陈文敏,龙玲玉,刘艳荣,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
Characteristics and Prognostic Significance of Ki-67 Expression at diagnosis in Adult t(8;21) Acute Myeloid Leukemia
DAO Feng-ting,YANG Lu,WANG Ya-zhe,CHANG Yan,YUAN Xiao-ying,LI Ling-di,CHEN Wen-min,LONG Ling-yu,LIU Yan-rong,QIN Ya-zhen()
Peking University Peoples’ Hospital, Peking University Institute of Hematology,National Clinical Research Center for Hematologic Disease, Beijing China,100044
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摘要:

目的: 研究成人t(8;21)急性髓系白血病(AML)初诊Ki-67抗原的表达特征及预后意义。方法: 采集2012年7月至2019年2月本院57例成人初诊t(8;21)AML患者的新鲜骨髓标本,采用流式细胞术(FCM)检测CD34和Ki-67抗原,分析Ki-67表达与患者初诊生物学特征、疗效及复发的关系。结果: 全部患者中,CD34 +Ki-67 +细胞比例的中位值为30.5%(范围:10.0%~65.8%);通过受试者工作特征(ROC)曲线确定CD34 +Ki-67 +细胞比例的最适分界阈值,CD34 +Ki-67 +细胞高比例与初诊c-KIT基因突变阳性及WT1转录本低水平均明显相关(P=0.001;P=0.042)。随访的36例患者中,CD34 +Ki-67 +高比例比低比例患者具有明显更高的1年累积复发(CIR)率(P=0.035);此外,初诊WT1转录本低水平和微小残留病(MRD)高水平(2个疗程巩固治疗后RUNX1-RUNX1T1转录本水平下降<3-log)均与更高的1年CIR率明显相关(P<0.0001;P=0.041),初诊c-KIT基因突变阳性和白细胞计数>10×10 9/L的患者分别有较高的1年CIR率趋势(P=0.091;P=0.054)。联合分组显示,MRD高水平同时CD34 +Ki-67 +细胞高比例的患者比其他患者具有明显更高的1年CIR率(P<0.0001)。 结论: 初诊骨髓高比例的CD34 +Ki-67 +可能是成人t(8;21)AML患者预后不良因素,MRD联合初诊CD34 +Ki-67 +细胞比例可能比单纯MRD更好地预测复发。

关键词: Ki-67抗原t(8;21)急性髓系白血病c-KITWT1微小残留病    
Abstract:

Objective: To investigate the characteristics and prognostic significance of Ki-67 antigen expression at diagnosis in adult t(8;21) acute myeloid leukemia (AML).Methods: Bone marrow samples of 57 adult t(8;21) AML patients were collected at diagnosis from July 2012 to February 2019 in our hospital, their frequencies of Ki-67 in CD34 + cells were detected by flow cytometry method, and the relationships between Ki-67 and the biological characteristics, therapeutic effect and relapse were analyzed. Results: Of all patients tested, the median percentage of CD34 +Ki-67 + cells were 30.5% (range: 10.0%~65.8%); A receiver operating characteristic (ROC) curve was used to identify the optimal cutoff levels of CD34 +Ki-67 + cells, higher frequencies of CD34 +Ki-67 + cells were significantly related to higher rate of c-KIT mutation and lower WT1 transcript level at diagnosis (P=0.001; P=0.042). Of all patients followed up, higher frequency of CD34 +Ki-67 + cells was significantly related to a higher 1-year cumulative incidence relapse (CIR) rate (P=0.035). In addition, both lower WT1 transcript level at diagnosis and higher level of minimal residual diseases (MRD, < 3-log reduction of the RUNX1-RUNX1T1 transcript level after the second consolidation therapy) were significantly related to a higher 1-year CIR rate (P<0.000 1; P=0.041), and patients with c-KIT mutation and white blood cell count>10×10 9/L at diagnosis tended to have higher 1-year CIR rates, respectively (P=0.091; P=0.054). Patients simultaneously with high frequency of CD34 +Ki-67 + cells and high MRD levels have a significantly higher 1-year CIR rate than others (P<0.000 1). Conclusion: In adult patients with t(8;21) AML, high frequency of CD34 +Ki-67 + cells at diagnosis may be a poor prognostic factor, combination of MRD levels and frequency of CD34 +Ki-67 + cells at diagnosis may better predict relapse than MRD alone.

Key words: Ki-67 antigen    t(8;21) AML    Proto-oncogene proteins c-KIT    WT1    Minimal residual diseases
收稿日期: 2019-08-22 出版日期: 2019-09-20
ZTFLH:  Q25  
基金资助: * 国家自然科学基金(81570130、81870125)
通讯作者: 秦亚溱     E-mail: qin2000@aliyun.com
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刀凤亭
杨璐
王亚哲
常艳
袁晓英
李玲娣
陈文敏
龙玲玉
刘艳荣
秦亚溱

引用本文:

刀凤亭,杨璐,王亚哲,常艳,袁晓英,李玲娣,陈文敏,龙玲玉,刘艳荣,秦亚溱. 成人t(8;21)急性髓系白血病患者初诊Ki-67的表达特征及预后意义 *[J]. 中国生物工程杂志, 2019, 39(9): 11-18.

DAO Feng-ting,YANG Lu,WANG Ya-zhe,CHANG Yan,YUAN Xiao-ying,LI Ling-di,CHEN Wen-min,LONG Ling-yu,LIU Yan-rong,QIN Ya-zhen. Characteristics and Prognostic Significance of Ki-67 Expression at diagnosis in Adult t(8;21) Acute Myeloid Leukemia. China Biotechnology, 2019, 39(9): 11-18.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.20190902        https://manu60.magtech.com.cn/biotech/CN/Y2019/V39/I9/11

图1  FCM各群细胞分析界定方式
参数 H-CD34+Ki-67+(n=35) L-CD34+Ki-67+(n=22) P
年龄
≤ 40 岁 16 14 0.28
> 40 岁 19 8
性别
16 14 0.28
19 8
白细胞计数
≤ 10×109/L 21 12 0.58
> 10×109/L 12 10
血红蛋白
≤80 g/L 18 14 0.58
>80 g/L 15 8
血小板
≤ 35×109/L 20 14 1.0
> 35×109/L 13 8
t(8;21)之外的其它异常核型(n=35)
10 10 0.089
12 3
c-KIT基因突变
阳性 24 5 0.001
阴性 11 17
WT1转录本水平
L-WT1 14 3 0.042
H-WT1 21 19
表1  患者初诊CD34+Ki-67+细胞比例与初诊生物学特征的关系
图2  初诊CD34+Ki-67+细胞比例、MRD水平及CD34+Ki-67+细胞比例联合MRD水平对患者1年CIR率的影响
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