弥漫性大 B 细胞淋巴瘤 (DLBCL) 是一种异质性疾病，其特征是部分患者表现出治疗耐药性和预后不良。基因组检测已广泛用于识别以 MYC、BCL2 和 BCL6 基因重排为特征的高危个体。这些患者通常会接受更积极的治疗；然而，他们的治疗结果仍然存在显着差异。本研究引入了源自基因表达谱的 MYC 特征评分 (MYCSS)，专门用于评估 DLBCL 患者的 MYC 过度激活。 MYCSS 在多个独立队列中进行了验证，以评估其根据 MYC 相关遗传和分子畸变对患者进行分层的能力，与传统 MYC 生物标志物相比，提高了预后评估的准确性。我们的结果表明，与专注于遗传畸变的传统 MYC 生物标志物相比，MYCSS 显着提高了预后准确性。更重要的是，我们发现近 50% 被传统 MYC 指标确定为高风险的患者实际上与那些没有 MYC 畸变的患者有着相似的生存前景。这些患者可能会受益于基于 GCB 的标准疗法，而不是更积极的治疗。 MYCSS 提供了一个强大的签名，可以识别高风险患者，有助于 DLBCL 的精准治疗，并最大程度地减少过度治疗的可能性。© 2024 英国血液学会和 John Wiley

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease characterized by a subset of patients who exhibit treatment resistance and poor prognoses. Genomic assays have been widely employed to identify high-risk individuals characterized by rearrangements in the MYC, BCL2 and BCL6 genes. These patients typically undergo more aggressive therapeutic treatments; however, there remains a significant variation in their treatment outcomes. This study introduces an MYC signature score (MYCSS) derived from gene expression profiles, specifically designed to evaluate MYC overactivation in DLBCL patients. MYCSS was validated across several independent cohorts to assess its ability to stratify patients based on MYC-related genetic and molecular aberrations, enhancing the accuracy of prognostic evaluations compared to conventional MYC biomarkers. Our results indicate that MYCSS significantly refines prognostic accuracy beyond that of conventional MYC biomarkers focused on genetic aberrations. More importantly, we found that nearly 50% of patients identified as high risk by traditional MYC metrics actually share similar survival prospects with those having no MYC aberrations. These patients may benefit from standard GCB-based therapies rather than more aggressive treatments. MYCSS provides a robust signature that identifies high-risk patients, aiding in the precision treatment of DLBCL, and minimizing the potential for overtreatment.© 2024 British Society for Haematology and John Wiley & Sons Ltd.