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 Waldenstr?m macroglobulinemia

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中文摘要：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 withIGHV 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.

外文摘要：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 withIGHV 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.

外文关键词：

Immunoglobulin heavy chain variableGenetic variantWaldenström macroglobulinemiaPrognosis

作者：

汤菁、夏奕、尹华、王莉、吴佳竹、陈睿泽、梁金花、朱华渊、范磊、李建勇、徐卫、李岭

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作者单位：

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

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

基金：

国家自然科学基金国家自然科学基金国家自然科学基金国家自然科学基金"重大新药创制"科技重大专项中国博士后科学基金江苏省科技厅社会发展项目江苏省医学重点人才项目江苏省博士后科学基金

项目编号：

817701668172010800281700193821701862018ZX097340072021M691336BE2017751ZDRCA20160222021K083A

出版年：

2023

DOI：

10.3760/cma.j.cn511374-20211214-00988

中华医学遗传学杂志

中华医学会

中华医学遗传学杂志

CSTPCDCSCD

影响因子：0.562

ISSN：1003-9406

年,卷(期)：2023.40(3)

参考文献量25