bcl-6、p53、c-myc基因异常在弥漫大B细胞淋巴瘤中的临床意义

Clinical significance of bcl-6, p53, c-myc aberrations in diffuse large B-cell lymphoma

目的 探讨bcl-6 、p53、c-myc基因异常的检测在弥漫大B细胞淋巴瘤（DLBCL）中的临床意义.方法 间期荧光原位杂交（I-FISH）方法检测59例DLBCL患者活体石蜡组织bcl-6、p53蛋白、c-myc基因异常的情况,同时以CHOP及R-CHOP方案化疗,评价疗效.观察bcl-6、p53蛋白、c-myc基因与化疗疗效及生存期的关系.结果 59例DLBCL中,p53丢失18例（30.5％）,bcl-6重排11例（18.6％）,c-myc重排5例（8.5％）.p53丢失阳性组化疗有效率（33.3％）明显低于阴性组（76.5％）（x2=9.560,P=0.002）. bcl-6基因重排阳性组的预后差于基因重排阴性组,但差异无统计学意义[总生存（OS）,P=0.107;无进展生存时间（PFS）,P=0.094]; p53基因丢失阳性组预后明显差于阴性组（OS,P=0.031;IPFS,P=0.028）;c-myc重排阳性组的预后差于基因重排阴性组,但差异无统计学意义（OS,P=0.163;PFS,P=0.167）.其中CHOP化疗组患者,p53基因丢失、c-myc重排阳性组的预后明显差于阴性组,差异有统计学意义（P值均＜ 0.05）;R-CHOP化疗组,bcl-6基因重排阳性组具有较差的预后意义（OS,P=0.003;PFS,P=0.007）.结论 bcl-6 、p53、c-myc基因异常与 DLBCL预后密切相关,可作为预测DLBCL的预后因素并指导治疗.

Objective To investigate aberrations of bcl-6,p53,c-myc genes in diffuse large B-cell lymphoma （DLBCL） and its clinical significance.Methods Interphase fluorescence in situ hybridization （I-FISH） was detected in 59 DLBCL patients in vivo tissue bcl-6,p53 protein,c-myc gene status.The patients were treated with CHOP or R-CHOP chemotheralpy,and the survival rates and treatment efficiency were compared.Results The p53 deletion was detected in 18 of the 59 cases （30.5 %）,bcl-6 rearrangement in 11 cases （18.6 %）,5 cases with c-myc rearrangement （8.5 %）.In the aspects of remission rate,p53 deletion positive group contained less advantage than negative ones （33.3 % vs 75.6 %,x2 =9.560,P =0.002）.The prognosis of bcl-6 gene rearrangement positive group different from negative group,but the difference was not statistically significant （OS,P =0.107; PFS,P =0.094）,p53 deletion positive patients was in significantly worse prognosis than the negative group （OS,P =0.031; PFS,P =0.028）,c-myc rearrangement positive group difference in gene rearrangement negative group,but the difference was not statistically significant （OS,P =0.163; PFS,P =0.167）.In the CHOP group,prognosis of p53 deletion,c-myc rearrangement positive group were significantly worse than the negative group,the difference was statistically significant （P 〈 0.05）.In R-CHOP group,the prognostic significance of bcl-6 gene rearrangement positive group were worse （OS,P =0.003; PFS,P =0.007）.Conclusion DLBCL patients with bcl-6,p53,c-myc genes aberrations are related with poor prognosis,and they can be used as prognostic factors for predicting DLBCL and guiding therapy.