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首页> 外文期刊>Blood: The Journal of the American Society of Hematology >MDM2 phenotypic and genotypic profiling, respective to TP53 genetic status, in diffuse large B-cell lymphoma patients treated with rituximab-CHOP immunochemotherapy: a report from the International DLBCL Rituximab-CHOP Consortium Program
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MDM2 phenotypic and genotypic profiling, respective to TP53 genetic status, in diffuse large B-cell lymphoma patients treated with rituximab-CHOP immunochemotherapy: a report from the International DLBCL Rituximab-CHOP Consortium Program

机译：利妥昔单抗-CHOP免疫化学疗法治疗的弥漫性大B细胞淋巴瘤患者中与TP53遗传状态相对应的MDM2表型和基因型谱：国际DLBCL利妥昔单抗-CHOP联合计划的报告

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摘要

MDM2 is a key negative regulator of the tumor suppressor p53, however, the prognostic significance of MDM2 overexpression in diffuse large B-cell lymphoma (DLBCL) has not been defined convincingly. In a p53 genetically-defined large cohort of de novo DLBCL patients treated with rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone (R-CHOP) chemotherapy, we assessed MDM2 and p53 expression by immunohistochemistry (n = 478), MDM2 gene amplification by fluorescence in situ hybridization (n = 364), and a single nucleotide polymorphism in the MDM2 promoter, SNP309, by SNP genotyping assay (n = 108). Our results show that MDM2 overexpression, unlike p53 overexpression, is not a significant prognostic factor in overall DLBCL. Both MDM2 and p53 overexpression do not predict for an adverse clinical outcome in patients with wild-type p53 but predicts for significantly poorer survival in patients with mutated p53. Variable p53 activities may ultimately determine the survival differences, as suggested by the gene expression profiling analysis. MDM2 amplification was observed in 3 of 364 (0.8%) patients with high MDM2 expression. The presence of SNP309 did not correlate with MDM2 expression and survival. This study indicates that evaluation of MDM2 and p53 expression correlating with TP53 genetic status is essential to assess their prognostic significance and is important for designing therapeutic strategies that target the MDM2-p53 interaction.
机译：MDM2是肿瘤抑制因子p53的关键负调控因子，但是，MDM2在弥漫性大B细胞淋巴瘤（DLBCL）中过表达的预后意义尚不确定。在接受利妥昔单抗，环磷酰胺，羟基柔红霉素，长春新碱和泼尼松（R-CHOP）化疗的p53基因从头定义的DLBCL大患者队列中，我们通过免疫组化方法（n = 478）评估了MDM2和p53的表达，通过免疫组化评估了MDM2基因的扩增荧光原位杂交（n = 364），以及通过SNP基因分型分析（n = 108）在MDM2启动子SNP309中具有单核苷酸多态性。我们的结果表明，与p53过表达不同，MDM2过表达不是总体DLBCL的重要预后因素。 MDM2和p53过表达均不能预测野生型p53患者的不良临床预后，但可以预测p53突变患者的生存期明显较差。如基因表达谱分析所表明的，可变的p53活性可能最终决定存活差异。在364名MDM2高表达患者中，有3名（0.8％）观察到MDM2扩增。 SNP309的存在与MDM2表达和生存无关。这项研究表明，评估与TP53遗传状态相关的MDM2和p53表达对于评估其预后意义至关重要，对于设计针对MDM2-p53相互作用的治疗策略也很重要。

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