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 theTP53gene, 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 ofTP53mutational status for prognostication and, in prospect, treatment stratification in DLBCL.
弥漫性大B细胞淋巴瘤（DLBCL）是最常见的淋巴系统恶性肿瘤，其本身具有高度异质性，包含多个生物学特征各异的亚型。近年来，基于指示不同转化途径的常见突变模式，研究者已提出多种新型DLBCL基因分型体系。然而，这些新型分类方法因操作复杂且成本高昂，尚未能纳入常规临床实践。在此背景下，TP53基因状态（约20-30%病例存在该基因突变或缺失）已成为DLBCL患者重要的预后指标，其预测价值显著区别于其他预后因素。TP53基因异常在具有里氏综合征基因组特征的DLBCL遗传亚型中尤为富集，这提示部分DLBCL可能源于隐匿性慢性淋巴细胞白血病样恶性肿瘤（如单克隆B淋巴细胞增多症）的转化。携带TP53突变的DLBCL患者（包括里氏综合征患者）预后极差，且对标准化学免疫治疗方案反应不佳。本文数据表明，有必要建立更完善且实用的DLBCL风险分层模型，并揭示了TP53突变状态在DLBCL预后评估及未来治疗分层中的应用潜力。
Molecular Subtypes and the Role of TP53 in Diffuse Large B-Cell Lymphoma and Richter Syndrome
肿瘤(癌症)患者之家