慢性淋巴细胞白血病患者典型模式B细胞受体的表达及临床预后意义  

Expression of stereotyped B-cell receptor and its clinical value in chronic lymphocytic leukemia

作　　者：于珍[1] 李增军[1] 易树华[1] 周可树[2] 郝牧[1] 李长虹[1] 齐军元[1] 邱录贵[1] 

机构地区：[1]中国医学科学院北京协和医学院血液学研究所血液病医院实验血液学国家重点实验室,天津300020 [2]郑州大学附属肿瘤医院河南省肿瘤医院

出　　处：《中华医学杂志》2011年第46期3267-3270,共4页National Medical Journal of China

基　　金：国家科技支撑计划项目（2008BAI61B01）;国际科技合作项目（2010DFB30270）;天津市科技支撑计划项目（09ZCGYSF01000、09ZCZDSF03800）

摘　　要：目的 探讨我国慢性淋巴细胞白血病（CLL）患者典型模式B细胞受体（stereotyped BCR）的表达情况及其预后价值.方法 应用多重PCR方法检测1992年4月至2010年4月中国医学科学院北京协和医学院血液学研究所116例CLL患者免疫球蛋白重链可变区（IGHV）片段使用情况及突变状态,应用多序列比对软件ClustalW2明确我国典型模式BCR的表达情况,并与CLL患者IGHV突变状态、细胞遗传学异常、生存和预后进行相关性分析.结果 共检测初诊CLL患者116例,102例成功测序,检出率87.9％.测序反应共得到73例患者的IGHV互补决定区3（CDR3）序列,19.2％（14例）CLL患者BCR为典型模式.与IGHV突变组相比,未突变组患者中典型模式BCR的发生率更高（40.9％比11.8％,P=0.005）.BCR为典型模式的CLL患者中17q-的发生率更高（33.3％比10.7％,P=0.045）.BCR为典型模式的CLL患者的中位无进展生存时间（PFS）较其他组为短（39个月比84个月,p =0.002）.结论 BCR为典型模式的CLL患者预后较差.典型模式BCR的存在表明肿瘤细胞曾面临同样的抗原选择过程,提示抗原选择与CLL的发生密切相关.Objective To investigate the expression pattern of stereotyped B-cell receptor（BCR）and its prognostic significance in Chinese chronic lymphocytic leukemia（CLL）patients and evaluate the relationship to other prognostic markers.Methods Multiplex polymerase chain reaction（PCR）was used to identify the immunoglobulin vaiiable heavy-chain（IGHV）segment and its mutation status in 116 CLLpatients from April 1992 to April 2010.For CDR3-driven clustering,all in-frame IGHV-D-J rearrangements were aligned by the multiple sequence alignment software ClustalW2.Results There were 102 of 116 samples from newly diagnosed CLL were successfully analyzed.IGHV CDR3 genes were identified in 73/102 cases.Fourteen patients（19.2%）carried stereotyped BCR.A high percentage of carried stereotyped BCR was observed in 1GHV non-mutated group versus mutated group（40.9% vs 11.8%,P =0.005）.Patients with stereotyped BCR had a higher frequency of deletion（17q）（33.3% vs 10.7%,P =0.045）.The median progression-free survival（PFS）in patients with stereotyped BCR was much shorter than other patients（39 vs 84 months,P =0.002）.Conclusion The patients with stereotyped BCR have a poor prognosis.It highlights the importance of immunoglobulin mediated stimulation in the development of CLL.

关 键 词：白血病 淋巴细胞 慢性 预后 典型模式B细胞受体 

分 类 号：R733.72[医药卫生—肿瘤]