iFISH技术检测多发性骨髓瘤遗传学异常及其临床意义

目的:采用iFISH技术了解多发性骨髓瘤染色体异常情况，分析染色体异常与多发性骨髓瘤部分临床资料、治疗效果及预后之间的关系。方法:采用组合探针（1q21、DLEU/RB1、p53、IGH）对94例初诊MM患者骨髓细胞进行iFISH检测，分析其细胞遗传学异常，探讨其与临床资料及治疗效果之间的关系，明确其预后价值。结果:94例患者中，74例（78.72%）检测出1种及1种以上细胞遗传学异常；其中1种异常的34例（34/74，45.95%），2种异常的15例（15/74，20.27%），25例存在3种及3种以上异常（25/74，33.78%）。其异常的比例从高到低分别为:p53缺失（45/74，60.81%），1q21扩增（44/74，59.46%），IGH重排（31/74，41.89%），DLEU/RB1缺失（28/74，37.84%）。分析发现，p53缺失与血小板计数、白蛋白及球蛋白水平有关，IGH重排与白蛋白及瘤细胞负荷有关，DLEU/RB1缺失与血红蛋白、血沉、白蛋白及球蛋白水平有关，未发现1q21扩增与各项临床指标之间的关系。将患者按照治疗方案分为VAD组和硼替佐米组，结果显示VAD组中iFISH阴性者的疗效明显优于iFISH阳性者，而在硼替佐米组未发现FISH阳性者和阴性者的疗效有差异。生存分析发现，IGH重排与总生存时间相关，而p53缺失与总生存时间和无病生存时间均明显相关，为MM患者的独立预后因素。结论:多数MM患者存在细胞遗传学异常；1q21扩增、p53缺失及IGH重排的发生率较高；细胞遗传学异常与多种不良临床指标相关，并与临床治疗反应性相关，存在异常者治疗效果欠佳，预后较差。

Detection of chromosome aberrations by iFISH in multiple myeloma and their clinical significance

Objective:To detect the chromosome aberrations in multiple myeloma (MM) patients using interphase fluorescence in situ hybridization (iFISH)，and to explore their clinical significance and prognostic value.Methods:94 newly diagnosed MM patients were enrolled and iFISH panel probes of IGH，DLEU/RB1，p53 and 1q21 were applied to detect 14q32 translocation，del(13q14)，del(17p13)，and 1q21 application，respectively.The thresholds were established using 15 patients without hematopoietic malignancies.Results:A total of 74 patients of the whole 94 patients (78.72%) exhibited abnormal iFISH results.del(17p13) had the highest occurrence rate with the percentage of 60.81%(45/74)，followed by 1q21 application (59.46%，44/74)，14q32 translocation (41.89%，31/74) and del(13q14)(37.84%，28/74).It showed that del(17p13) was related with platelet count，albumin and globulin levels，14q32 translocation was related with albumin and myeloma cell burden，del(13q14) exhibited a correlation with hemoglobin，erythrocyte sedimentation rate，albumin and globulin levels，while 1q21 application did not show any relations with these clinicopathological parameters.When patients were grouped by the therapeutic regimen，it showed that those whose iFISH were positive had worse treatment responses in VAD group compared with those negative，whereas it did not show any differences in bortezomib group.Moreover，14q32 translocation was shown to related with patients' overall survival，and del(17p13) was predicted to be independently associated with patients'overall survival and progression free survival.Conclusion:Chromosome aberrations exist in majority of myeloma patients with high occurrence rate of del(17p13)，1q21 application and 14q32 translocation，which indicated unfavorable clinical features and poor outcome.