PDF(Pubmed)
Abstract：
Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid malignancy and a heterogeneous entity comprised of several biologically distinct subtypes. Recently, novel genetic classifications of DLBCL have been resolved based on common mutational patterns indicative of distinct pathways of transformation. However, the complicated and costly nature of the novel classifiers has precluded their inclusion into routine practice. In view of this, the status of the TP53 gene, which is mutated or deleted in 20-30% of the cases, has emerged as an important prognostic factor for DLBCL patients, setting itself apart from other predictors. TP53 genetic lesions are particularly enriched in a genetic subtype of DLBCL that shares genomic features with Richter Syndrome, highlighting the possibility of a subset of DLBCL arising from the transformation of an occult chronic lymphocytic leukemia-like malignancy, such as monoclonal B-cell lymphocytosis. Patients with TP53-mutated DLBCL, including those with Richter Syndrome, have a particularly poor prognosis and display inferior responses to standard chemoimmunotherapy regimens. The data presented in this manuscript argue for the need for improved and more practical risk-stratification models for patients with DLBCL and show the potential for the use of TP53 mutational status for prognostication and, in prospect, treatment stratification in DLBCL.
摘要：
弥漫性大B细胞淋巴瘤（DLBCL）是最常见的淋巴恶性肿瘤，是由几种生物学上不同的亚型组成的异质实体。最近,DLBCL的新遗传分类已经基于表明不同转化途径的常见突变模式得到解决。然而,新颖分类器的复杂和昂贵的性质已排除了将其纳入常规实践的可能性。鉴于此,TP53基因的状态，在20-30%的病例中突变或缺失，已成为DLBCL患者的重要预后因素，将自己与其他预测因素区分开来。TP53基因病变在DLBCL的遗传亚型中特别丰富，该亚型与Richter综合征共享基因组特征，强调了由隐匿性慢性淋巴细胞白血病样恶性肿瘤的转化引起的DLBCL子集的可能性，如单克隆B细胞淋巴细胞增多症。TP53突变的DLBCL患者，包括里氏综合症患者,预后特别差，对标准化学免疫疗法的反应较差。本手稿中提供的数据认为DLBCL患者需要改进和更实用的风险分层模型，并显示了使用TP53突变状态进行预后的潜力，在前景中，DLBCL的治疗分层。
