【摘要】 目的:探讨阳性调控区Ⅰ蛋白(PRDM1)在弥漫大B细胞淋巴瘤中的表达和预后意义。方法:采用免疫组织化学方法根据CD10、BCL6和IRF4的表达将82例弥漫大B细胞淋巴瘤患者分为生发中心和非生发中心型,显微切割联合RT-PCR和W estern杂交方法检测患者PRDM1的表达情况并观察对CHOP和美罗华联合CHOP方案(R-CHOP)治疗后生存期的影响;利用半定量RT-PCR和W estern杂交观察PRDM1在B细胞淋巴瘤Namalwa细胞株中表达和美罗华、阿霉素以及美罗华联合阿霉素对其表达的影响,利用ELISA方法观察PRDM1表达与NF-κB活性的关系。统计分析软件SAS 8.2,P值小于0.05有统计学意义。结果:PRDM1存在α和β两种亚型,显著表达于弥漫大B细胞淋巴瘤非生发中心亚型的肿瘤细胞(73.5%比38.8%,39.4%比6.1%;P=0.0020和P=0.0009),而PRDM1β在CHOP方案治疗的非生发中心型患者中与短生存期相关,但在R-CHOP方案治疗组中未显示相关性;Namalwa细胞株中表达PRDM1β,美罗华和美罗华联合阿霉素均能够抑制PRDM1β表达,同时伴随NF-κB的失活。结论:PRDM1显著表达在弥漫大B细胞淋巴瘤非生发中心亚型中,PRDM1β可能与疾病的不良预后有关。更多还原

【Abstract】 Objective: To explore PRDM1 expression and prognostic value in patients with diffuse large B-cell lymphoma.Methods: 82 patients with diffuse large B-cell lymphoma(DLBCL) were divided into germinal center and non-germinal center subtypes according CD10,BCL6 and IRF4 expression with immunohistichemistry(IHC).Laser microdissectin combined with reverse transcription-polymerase chain reaction(RT-PCR) and Western blot were used to detect PRDM1 expressionin two subtypes of DLBCL patients.Results: Correlation of PRDM1 expression with survival was analyzed by SAS software in CHOP and rituximab combined with CHOP(R-CHOP) treatment.We observed PRDM1 expression in Namalwa cell line and its alteration after being treated by rituximab,doxorubicin and rituximab plus doxorubicin with semiquantitative RT-PCR and Western blot.Enzyme-linked immunosobent assay(ELISA) was applied to assess the relation between PRDM1 and nuclear factor(NF)-kappa B activity.It was significant when P value was less than 0.05.Results: There exists PRDM1α and β isoforms which dorminantly expressed in lymphoma cells of non-germinal center subtype(73.5% vs 38.8%,39.4% vs6.1%;P=0.0020 and P=0.0009),moreover,PRDM1β predicted shorter survival in CHOP treatment,not in R-CHOP.PRDM1β also expressed in Namalwa cell line and could be downregulated after treating with rituximab and rituximab plus doxorubicin,accompanying to NF-kB inactivity.Conclusion: PRDM1 dorminantly expresses in lymphoma cells of non-germinal center subtype and PRDM1β may indicate poor prognosis in DLBCL patients.更多还原