成人急性淋巴细胞白血病4种特异性靶抗原的特征研究  

Characteristics of 4 Specific Target Antigens in Adult Acute Lymphoblastic Leukemia

作　　者：林忠琨[1] 张闰[1] 葛峥[1] 刘娟[1] 吴雨洁[1] 郭星[1] 乔纯[1] 仇海荣[1] 李建勇[1] 

机构地区：[1]南京医科大学第一附属医院血液科,江苏南京210029

出　　处：《中国实验血液学杂志》2013年第2期289-295,共7页Journal of Experimental Hematology

基　　金：国家自然科学基金面上项目(30973376;81270613);江苏省自然科学基金(BK2009442);江苏省医学重点人才(RC2011077);中国博士后科学基金特别资助(201003598);中国博士后科学基金(20090461134);教育部"留学回国人员科研启动基金"(第39批);江苏省"六大人才高峰"资助(2010-WS-024);南京市留学回国人员科技活动项目择优资助(2009)

摘　　要：本研究针对成人急性淋巴细胞白血病(ALL)抗体免疫治疗的主要4种特异性靶抗原(CD19、CD20、CD22和CD33),深入探究其临床和预后特征,探讨针对这些靶抗原的新型靶向药物应用于成人ALL治疗的临床依据和价值。对220例成人ALL患者采用四色流式细胞仪进行免疫表型分析,采用常规细胞遗传学、荧光原位杂交、实时定量PCR和巢式PCR扩增及DNA测序等技术进行细胞学和分子遗传学、分子生物学指标检测。结果显示,CD19阳性(CD19+)组女性和60岁以上老年患者比例高于CD19阴性(CD19-)组(46.4%vs 23.4%,P=0.006)(14.4%vs.2.1%,P=0.022),CD19+伴CD33表达增高(47.8%vs.12.0%,P<0.01),遗传学高危组患者比例显著增高(55.8%vs.20.8%,P<0.01),Philadelphia染色体阳性(Ph+)发生率高(35.3%vs.7.9%)(P<0.01);CD20+组伴CD13+低于CD20-组(31.6%vs.67.1%,P<0.01),CD20+无显著预后意义;在B-ALL患者中,CD22+比CD22-组12月复发率增高(93.9%vs.57.1%,P<0.05);CD33+组Ph+率显著增高(43.5%vs.19.4%,P<0.01),CD33+与Ph+之间有显著相关性(相关系数=0.261,P<0.01)。结论:本研究对CD19、CD20、CD22和CD33这些特异性靶抗原特征的深入分析,有助于指导临床正确把握抗体免疫治疗的适应症和应用时机,使患者最大程度获益。This study was aimed to investigate clinical and prognostic significances of 4 target antigens （CD19, CD20, CD22 and CD33 ） for antibody-based immunotherapy and to evaluate the applications of these antibody-based target therapy to adult acute lymphoblastic leukemia （ALL）. The immunophenotype of 220 adult patients with ALL were analyzed by four-color flow Cytometry, and cytogenetic and molecular parameters were detected by conventional cytogenetics, fluorescence in situ hybridization, real-time quantitative PCR, nested PCR and DNA sequencing. The results showed that CD19 positive （CD19＋ ） cases were more in female （46.4% vs. 23.4% ,P = 0. 006）, elderly patients aged 〉 60 years （ 14.4% vs. 2.1% ,P = 0.022 ）, CD33 ＋ co-expression cases （47.8% vs. 12.0%, P = 0.001 ） and genetic high-risk group （ 55.8 % vs. 20.8 %, P = 0. 002 ） compared with CD19 negative （ CD19 - ） cases; CD20＋ cases had lower co-expression of CD13 than CD20- cases （31.6% vs. 67.1%, P=0.000） and no significant prognostic indications for CD20 ＋ was observed; CD22 ＋ cases had higher relapse rate at 12-month than CD22- cases（93.9% vs. 57.1% ,P =0. 041 ） in B-ALL patients; CD33 ＋ cases had higher incidence of Ph ＋ than CD33 - cases（43.5% vs. 19. 4%, P = 0. 007 ） and significantly correlated with Ph ＋ （ r = 0. 261, P = 0. 006 ）. It is concluded that elucidation of the characteristics of the target antigens （CD19, CD20, CD22, CD33 ） used for antibody-based immunotherapy will help hematologists making the correct decision whether and when to use these antibody-based target therapies.

关 键 词：成人 急性淋巴细胞白血病 CD19 CD20 CD22 CD33 

分 类 号：R733.71[医药卫生—肿瘤]