中文摘要：

目的探讨新型遗传学指标lp21位点缺失在多发性骨髓瘤（MM）患者中的缺失率、临床相关性和预后意义。方法以接受沙利度胺为基础治疗的78例初治MM患者为研究对象，以定位于lp21位点的细胞分裂周期基因14A（cell division cycle 14A，CDC l4A）的BAC克隆制备位点特异性荧光探针，采用荧光原位杂交技术检测骨髓CDl38阳性细胞，统计lp21位点的缺失率和缺失细胞比例，并结合患者的临床资料进行预后分析。结果78例MM患者中，男51例，女27例，中位年龄59（42～81）岁。lp21位点缺失患者18例（23．1％），扩增患者4例（5．1％），扩增率明显低于缺失率（P=0.001）。临床相关性分析显示lp21位点缺失和肾损害（肌酐≥177μmol／L，P=0．014））、骨髓浆细胞比例≥0．500（P=0．000）、LDH≥220u／L（P=0．010）和B：微球蛋白≥5．5mg／L（P=-0．022）呈正相关。中位随访时间15．0（1．0～53．5）个月，lp21位点缺失患者中位无进展生存（PFS）和总生存（OS）时间分别为（12．0：62，7）个月和（14．0：63．4）个月，无lp21位点缺失患者中位PFS和OS时间分别为（30．0：68．0）个月和（38．5：61．8）个月，两组比较差异有统计学意义（P值均为0．000）。将lp21位点缺失和影响本组患者PFS和OS的复杂核型、高LDH、肾损害和17p13缺失等因素共同纳入多因素分析，结果显示lp21位点缺失仍然是PFS（HR：3．312，95％CI：1．095-10．017，P=0．034）和OS（HR：4．961，95％CI：1．487～16．552，P=0．009）的独立影响因素。结论lp21位点缺失是对MM患者预后有重要影响的遗传学指标。

英文摘要：

Objective To explore the deletion rate, clinical correlation and prognostic significance of lp21 deletion, a novel genetic prognostic index, in patients with multiple myeloma （MM）. Methods The interphase fluorescence in situ hybridization （I-FISH） was performed on purified CD138＋plasma cells from 78 newly diagnosed patients from Sep 2007 to Sep 2012 receiving thalidomide-based chemotherapy by using BAC probe covered lp21.2 region that contains the human cell division cycle 14A （HCDC14A） gene. Deletion rate, the cell percentage of deletion, clinical relevance and prognostic significance were analyzed in myeloma patients. Results Among 78 patients, there were 51 males and 27 females, the median age was 59 （42-81）. The deletion rate of lp21.2 was 23.1%. Some patients had amplification （amp） of lp with amp rate of 5.1% in lp21.2, the amp rate was significantly lower than the deletion rate （P-0.001 ）. l p21.2 deletion was positively correlated with renal lesion （Cr≥177 μmol/L）, high percentage of plasma cells in bone marrow, high LDH （≥220 U/L） and high [32-MG （P=0.014, 0.000, 0.010 and 0.022, respectively）. With a median follow-up time of 15.0 （1.0-53.5） months, the estimated median progression- free survival （PFS）and overall survival （OS）time for patients with lp21 deletion was （12.0±2.7） and （14.0±3.4） months, however those were （30.0±8.0） and （38.5±1.8） months in patients without lp21 deletion, respectively （P=0.000）. On multivariate analysis, which included complex karyotype, LDH≥220U/L, renal lesion and del （17p13）, lp21 deletion remained as an independent risk factor for PFS （HR. 3.312, 95% CI. 1.095- 10.017, P=0.034） and OS （HR： 4.961, 95% CI： 1.487-16.552, P=0.009）. Conelusion lp21 deletion is an important genetic prognosis indicator in multiple myeloma patients.