华氏巨球蛋白血症患者44例免疫球蛋白重链序列使用特征的分析  

Clonotypic analysis of immunoglobulin heavy chain sequences among 44 patients with Waldenström macroglobulinemia

作　　者：汤菁 夏奕 尹华 王莉[1] 吴佳竹 陈睿泽 梁金花 朱华渊 范磊 李建勇 徐卫 Tang Jing;Xia Yi;Yin Hua;Wang Li;Wu Jiazhu;Chen Ruize;Liang Jinhua;Zhu Huayuan;Fan Lei;Li Jianyong;Xu Wei(Department of Hematology,The First Affiliated Hospital of Nanjing Medical University(Jiangsu Provincial Hospital),Nanjing,Jiangsu 210036,China)

机构地区：[1]南京医科大学第一附属医院(江苏省人民医院)血液科,南京210036

出　　处：《中华医学遗传学杂志》2023年第3期263-268,共6页Chinese Journal of Medical Genetics

基　　金：国家自然科学基金(81770166、81720108002、81700193、82170186);重大新药创新科技重大专项(2018ZX09734007);中国博士后科学基金(2021M691336);江苏省科技厅社会发展项目-临床前沿技术(BE2017751);江苏省医学重点人才项目(ZDRCA2016022);江苏省博士后科学基金(2021K083A)。

摘　　要：目的探讨免疫球蛋白重链可变区(IGHV)基因的变异状态与华氏巨球蛋白血症(WM)患者预后的相关性。方法采集2010年12月至2020年12月在江苏省人民医院初诊的44例WM患者的血液和/或骨髓样本,通过直接测序确定主克隆并进行免疫球蛋白重链(IGH)基因的序列分析,描述WM患者IGHV-IGHD-IGHJ基因的使用特征。结果在44例患者中,IGHV3基因家族的使用率最高,该结果与中国医学科学院血液病研究所的数据相似,主要使用的片段为IGHV3-23(20.45%vs.15.44%)及IGHV3-74(11.36%vs.7.35%),其次为IGHV4基因家族(15.91%vs.24.26%)。但使用IGHV4家族与预后无相关性。以98%作为IGHV变异状态的截断值,仅5例患者IGHV无变异,且与预后无相关性。根据X-tile分析,选择将92.6%作为WM患者IGHV变异状态的截断值,26例(59.1%)IGHV无变异患者的血清乳酸脱氢酶增高(P<0.05),无进展生存期(P<0.05)及OS(P<0.05)与IGHV变异组相比均显著缩短。结论患者IGHV-IGHD-IGHJ的使用特征与中国医学科学院血液病研究所的数据相似,但使用IGHV4家族与预后无相关性。此外,98%可能并不适用于区分WM患者的IGHV变异状态。Objective To analyze the correlation between the mutational status of immunoglobulin heavy chain variable(IGHV)gene with the prognosis of patients with Waldenström macroglobulinemia(WM).Methods Immunoglobulin heavy chain gene(IGH)clonotypic sequence analysis was carried out to assess the mutational status of IGHV in the blood and/or bone marrow samples from 44 WM patients.The usage characteristics of IGHV-IGHD-IGHJ gene was explored.Results The most common IGHV subgroup was IGHV3,which was similar to the data from the Institute of Hematology of chinese Academy of Medical Science.IGHV3-23(20.45%vs.15.44%)and IGHV3-74(11.36%vs.7.35%)were the main fragments used,which was followed by IGHV4 gene family(15.91%vs.24.26%).However,no significant correlation was found between the IGHV4 usage and the prognosis of the patients.Should 98%be taken as the cut-off value for the IGHV mutation status,only 5 patients had no IGHV variant,and there was no correlation with the prognosis.Based on the X-tile analysis,92.6%was re-selected as the cut-off value for the IGHV variant status in such patients.LDH was increased in 26 patients(59.1%)without IGHV variant(P<0.05),progression-free survival(P<0.05)and overall survival(P<0.05)were significantly shorter compared with those with IGHV variants.Conclusion The usage characteristics of IGHV-IGHD-IGHJ in our patients was similar to reported by the Institute of Hematology of chinese Academy of Medical Science,albeit that no correlation was found between the IGHV4 usage and the prognosis of the patients.Furthermore,98%may not be appropriate for distinguishing the IGHV variant status in WM patients.

关 键 词：免疫球蛋白重链可变区 基因变异 华氏巨球蛋白血症 预后 

分 类 号：R553[医药卫生—血液循环系统疾病]