脾边缘区淋巴瘤患者IGHV突变状态分析  

IGHV mutational statue in patients with splenic marginal zone lymphoma

作　　者：杨文娟 于珍 吕瑞 李增军 李姮 熊文婕 易树华 刘薇 邱录贵 

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,天津300020

出　　处：《中华血液学杂志》2016年第9期774-778,共5页Chinese Journal of Hematology

基　　金：国家自然科学基金（81370632）

摘　　要：目的研究脾边缘区淋巴瘤（SMZL）患者免疫球蛋白重链可变区（IGHV）基因突变状态及典型模式的分布情况，并与国外报道的数据进行对比，以探讨其差异。方法对40例SMZL患者资料进行回顾性分析。采用克隆测序法检测IGHV的VDJ序列并进行比对及聚类分析，明确是否存在B细胞受体的典型模式，分析IGHV突变患者与未突变患者的临床特征。结果40例患者中，IGHV突变者30例（75．0％），未突变者10例（25．0％），两者比例与国外报道相当。在V区基因，V2-70的使用频率高于同外报道（10．3％对0．8％，P=0．002），而V3-23明显减低（2．6％对18．0％，P=0．006）。在D区基因中，D2-21和D6-13均高于国外报道（17．9％对2．3％，12．8％对3．8％，P值分别为0．000、0．046）。40例患者中发现1对新的典型模式，同时SMZL特异性的V1—2基因使用频率也最高（25．6％）。与IGHV突变组相比，未突变组患者的IgG、IgA表达水平显著增高[10．70（5．28～15．50）g／L对12．90（7．71～23．50）g／L，1．06（0．21～3．13）g／L对1．66（0．81～2．93）g／L，P值分别为0．038、0．040）]，2例17p缺失患者的IGHV均呈未突变状态。与IGHV未突变组相比，突变组患者的无进展生存期显著延长（P=0．009），但总生存期差异无统计学意义（P=-0．430）。结论在SMZL患者中，IGHV突变与未突变患者比例与国外报道相当，但V区和D区基因的使用频率仍存在差异，而且VI-2基因的使用呈现疾病特异性，同时发现1例新的典型模式。IGHV突变可降低患者的IgG、IgA表达水平。Objective To investigate the IGHV mutational status and its differences from Caucasian in splenic marginal zone lymphoma （SMZL）. Methods A retrospective study on 40 SMZL cases were performed to detect the V-D-J sequence of IGHV by plasmid cloning sequencing, comparing the data with the most homologous germ line V sequence in database, identifying the stereotype of patients through cluster analysis and alignment. The clinical and laboratory characteristics were compared between the patients with IGHV mutation and without mutations. Results In SMZL patients, the proportion of IGHV mutations was 75%, consistent with data from Caucasian. In V region, the usage of V3-23 subtype was lower in Chinese patients compared with Caucasian （2.6% vs 18.0%, P=-0.006）, whereas the V2-70 subtype was used with high proportion （10.3% vs 0.8%, P=0.002）. In D region, the D2-21 and D6-13 gene were used frequently （ 17.9% vs 2.3%, P〈0.001; 12.8% vs 3.8%, P=0.046）. One new stereotype was found, and the SMZL-biased V1-2 gene was mostly used （25.6%）. The levels of lgG and IgA were significantly increased in IGHV without mutations as compared with mutations ~ 10.70 （ 5.28-15.50 ） g/L vs l 2.90 （ 7.71- 23.50） g/L, 1.06 （0.21-3.13）g/L vs 1.66 （0.81-2.93）g/L, P=0.038, 0.0401. The only two 17p deletion patients were IGHV without mutaions. The progression free survival （PFS） was significantly prolonged in IGHV mutations （P=-0.009）, and there was no significant difference regarding to the overall survivalbetween the two subgroups （P=0.430）. Conclusion The proportion of IGHV mutaions was similar to the data in Caucasian. There was disparity in the usage of V and D regions between Chinese and Caucasian, and the SMZL-biased V1-2 gene were used more frequently in Chinese patients. One new stereotype was identified. In the IGHV without mutations group, the levels of IgG and IgA were significantly increased.

关 键 词：淋巴瘤 B细胞 边缘区 免疫球蛋白重链 突变 受体 抗原 B细胞 

分 类 号：R733.2[医药卫生—肿瘤]