高表达CD123的CD34＋CD19＋细胞为Ph染色体阳性急性淋巴细胞白血病复发预测的新标记  

CD34^+ CD19^+ Cells with CD123 Overexpression Are A Novel Prognostic Marker in Ph Chromosome-positive Acute Lymphoblastic Leukemia

作　　者：孔圆[1,2] 黄晓军[1,2,3] 郝乐[1,2] 秦亚溱[1,2] 江倩[1,2] 江浩[1,2] 刘艳荣[1,2] 

机构地区：[1]北京大学人民医院 [2]北京大学血液病研究所,造血干细胞移植治疗血液病北京市重点实验室,北京100044 [3]北京大学,清华大学生命科学联合中心,北京100871

出　　处：《中国实验血液学杂志》2014年第1期6-10,共5页Journal of Experimental Hematology

基　　金：国家重大科学仪器设备开发专项(2011YQ03013407);国家自然科学基金项目(81370638);北京市科技计划项目(Z111107067311070)

摘　　要：本研究探讨CD123在成人Ph染色体阳性急性淋巴细胞白血病(Ph chromosome-positive acute lymphoblastic leukemia,Ph+ALL)患者CD34+CD19+细胞上的表达特点及其在复发预测中的作用。2010年1月-2012年4月北京大学血液病研究所经规范化诊治的49例18-60岁初诊Ph+ALL患者纳入本研究,在初诊及治疗后不同时间点通过多色流式细胞术监测CD34+CD19+细胞上CD123的荧光强度及表达比例,同时利用实时定量聚合酶链式反应(real-time quantitative polymerase chain reaction,RQ-PCR)监测BCR-ABL1融合基因变化。与正常B祖细胞相比,获得完全缓解后任意时间点骨髓标本中异常高表达CD123的CD34+CD19+细胞大于10个定义为免疫残留阳性(FCM阳性)。结果表明,①初诊及复发Ph+ALL患者CD34+CD19+细胞上CD123的平均荧光强度(mean fluoresce intensity,MFI)〔8.52(3.71-32.35)vs 8.93(4.79-29.74)vs 1.31(0.21-1.75),P<0.05〕,以及异常高表达CD123的CD34+CD19+细胞比例〔84.63%(55.07%-99.96%)vs 84.50%(57.68%-99.80%)vs 0.99%(0.45%-1.83%),P<0.05〕均显著高于健康供者的正常B祖细胞。入组的全部初诊及复发Ph+ALL患者的CD34+CD19+细胞均高表达CD123。②多色流式细胞术监测异常高表达CD123的CD34+CD19+细胞和RQ-PCR检测BCR-ABL1融合基因的结果之间具有良好的相关性(n=49例,360对,Spearman r=0.90,P<0.0001)。③13例复发患者中有11例在复发前3个月MRD监测表明,在复发前中位时间60(30-73)天均检出FCM阳性。结论:通过多色流式细胞术检测异常高表达CD123的CD34+CD19+细胞可与RQ-PCR检测BCR-ABL1融合基因互为补充,共同应用于Ph+ALL患者的MRD监测以及复发预测。This study was aimed to investigate the characteristics of CD123 expression on CD34 ＋ CDl9 ＋ cells and its prognostic significance as a novel MRD biomarker in Philadelphia chromosome-positive acute lymphoblastic leukemia （Ph ＋ ALL） patients.Consecutive newly diagnosed Ph ＋ ALL patients （n =49） in Peking University Institute of Hematology from January 2010 to April 2012 were prospectively enrolled in this study.At diagnosis and different time points during treatment,CD123 expression on CD34 ＋ CD19 ＋ cells was examined by multiparameter flow cytometry （MFC）.More than 10 CD34 ＋ CD19 ＋ cells with CDl23 overexpression in bone marrow samples after complete remission were defined as FCM positive （FCM ＋）.The BCR-ABL1 transcript was detected by real-time quantitative polymerase chain reaction （RQ-PCR） concurrently.The results showed that mean fluorescence intensity of CD123 on CD34＋ CD19 ＋ cells in newly diagnosed Ph ＋ ALL and relapsed Ph ＋ ALL patients was significantly higher than that of normal B-cell progenitors [8.52 （3.71-32.35） vs 8.93 （4.79-29.74） vs 1.31 （0.21-1.75）,P ＜ 0.05].In addition,ratio of the CD34 ＋CD19 ＋ cells with CD123 overexpression in newly diagnosed Ph ＋ ALL and relapsed Ph＋ ALL patients were significantly higher than that of normal B-cell progenitors [84.63％ （55.07％-99.96％） vs 84.50％ （57.68％-99.80％） vs 0.99％ （0.45 ％-1.83 ％）,P ＜ 0.05].CD34 ＋ CD19 ＋ cells with CD123 overexpression were detected in all newly diagnosed and relapsed Ph ＋ ALL patients.A good correlation was found between the MRD results of CD34 ＋ CD19 ＋ cells with CD123 overexpression detected by MFC and that detected by RQ-PCR （n =360 pairs,Spearman r =0.90,P ＜0.0001）.Among 13 cases relapsed during follow up,11 cases of them were detected by FCM＋ at a median time of 60 （30-73） days before the recurrence.It is concluded that as a complementary to RQ-PCR,detection of the CD34 ＋CD19 ＋ cells with CD123 overexpression

关 键 词：CD123 CD34+ CD19+细胞 急性淋巴细胞白血病 PH染色体 

分 类 号：R733.71[医药卫生—肿瘤]