间期荧光原位杂交检测多发性骨髓瘤并临床分析  

Study on chromosomal aberrations in multiple myeloma patients by interphase fluorescence in situ hybridization and their association with clinical features

作　　者：郭力[1] 李文君[1] 侯明[1] 孙建芝[1] 邵琳琳[1] 马道新[1] 王淑康[2] 

机构地区：[1]山东大学齐鲁医院血液科,济南250012 [2]山东大学公共卫生学院

出　　处：《临床血液学杂志》2010年第5期523-526,529,共5页Journal of Clinical Hematology

基　　金：国家自然科学基金(No:30600259306006803077092230570779);国家"973"资助项目(No:2006CB503803);教育部全国优秀博士论文专项基金(No:200561);新世纪优秀人才支持计划(No:NCET-07-0514);教育部科学技术研究重点项目(No:109097);卫生部临床学科重点项目(No:2007-2009);国家卫生行业公益性科研专项(No:200802031);教育部科技创新工程重大项目培育资金项目(No:704030);教育部科技创新工程重大项目培育资金项目(No:704030);山东省科技发展计划(No:2005BS03022;Q2008C07;BS2009SW014);泰山学者岗位基金

摘　　要：目的:了解多发性骨髓瘤常见染色体异常情况及其与各项临床指标的关系,探讨有效预后指标。方法:运用IgH、RB1、D13S319、p53及1q21 5种序列特异性探针,利用间期荧光原位杂交技术(I-FISH),以10例正常对照的骨髓建立各探针的检测阈值,检测结果大于阈值为阳性,小于阈值为阴性。然后对17例染色体核型分析阴性的多发性骨髓瘤患者进行检测。结果:①IgH、RB1、D13S319、p53及1q21 5种探针的阈值分别为:2.75%、2.65%、2.87%、2.94%和3.23%。②17例患者中,IgH及RB1检测到17/17例阳性,D13S319、1q21及p53检测阳性例数分别为16/17、14/17、12/17,且p53缺失与1q21扩增间、RB1缺失与D13D319缺失间均呈显著正相关(分别为r=0.688 2,P<0.01;r=0.603 2,P<0.05)。③IgH易位发生率高的患者骨髓浆细胞率较高(r=0.587 6,P<0.05);D13S319缺失与外周血肌酐水平正相关(r=0.534 1,P<0.05);p53缺失阳性细胞率与C反应蛋白水平及年龄呈显著负相关(r=-0.900 0,P<0.05;r=-0.503 4,P<0.05);1q21扩增的阳性细胞率与年龄呈显著负相关(r=-0.555 5,P<0.05)。p53阳性与阴性患者间ISS分期差异有统计学意义(P<0.05),1q21扩增阳性与阴性患者在是否有溶骨性破坏、疾病状态(稳定、进展、死亡)方面差异有统计学意义(P<0.05)。结论:I-FISH技术的应用显著提高了多发性骨髓瘤染色体异常检出率及准确度,对于该疾病的评估预后及相关研究具有积极意义。Objective：To investigate the genetic abnormality in multiple myeloma（MM） patients and its relationship with clinical features and prognosis.Method：With the application of interphase fluorescence in situ hybridization（I-FISH）,sequence-specific DNA probes（IgH,RB1,D13S319,p53 and 1q21） were applied to detect 14q32 rearrangement,del（13q14）,del（17p13）,and gain of 1q21.Seventeen MM patients with negative conventional cytogenetics were enrolled in this study.The threshold was established using 10 controls without hematopoietic malignancies.Result：Compared with the threshold control,all of the 17 MM patients showed cytogenetic abnormalities.IgH and RB1 were found abnormal in all these 17 cases,while 16/17 abnormal cases for D13S319,and 14/17 abnormal cases,12/17 abnormal cases for 1q21 and p53 respectively.There was significant correlation between the aberration of p53 and 1q21 of the patients.These cytogenetic abnormalities were found associated with some of the clinical behavior and prognosis of MM,such as age,the percentage of plasma cells in bone marrow,the value of plasma creatinine,and the occupation of the bone marrow.Conclusion：I-FISH is a rapid and sensitive technique to refine chromosome aberrations in MM.The specific detection for genomic features of MM was proved to be correlative with its clinicopathologic characteristics and the prognosis.

关 键 词：多发性骨髓瘤 原位杂交 荧光 检测 

分 类 号：R733.3[医药卫生—肿瘤]