Division of Hematology, Mayo Clinic, Rochester, MN, USA.
Division of Lymphoma, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA.
Blood Cancer J. 2019 May 16;9(6):48. doi: 10.1038/s41408-019-0208-6.
Precision medicine is modernizing strategies for clinical study design to help improve diagnoses guiding individualized treatment based on genetic or phenotypic characteristics that discriminate between patients with similar clinical presentations. Methodology to personalize treatment choices is being increasingly employed in clinical trials, yielding favorable correlations with improved response rates and survival. In patients with diffuse large B-cell lymphoma (DLBCL), disease characteristics and outcomes may vary widely, underscoring the importance of patient classification through identification of sensitive prognostic features. The discovery of distinct DLBCL molecular subtypes based on cell of origin (COO) is redefining the prognosis and treatment of this heterogeneous cancer. Owing to significant molecular and clinical differences between activated B-cell-like (ABC)- and germinal center B-cell-like (GCB)-DLBCL subtypes, COO identification offers opportunities to optimize treatment selection. Widespread adoption of COO classification would greatly improve treatment and prognosis; however, limitations in interlaboratory concordance between immunohistochemistry techniques, cost, and availability of gene expression profiling tools undermine universal integration in the clinical setting. With advanced methodology to determine COO in a real-world clinical setting, therapies targeted to specific subtypes are under development. The focus here is to review applications of precision medicine exemplified by COO determination in DLBCL patients.
精准医学正在使临床研究设计策略现代化，以帮助改善诊断，根据区分具有相似临床表现的患者的遗传或表型特征指导个体化治疗。个性化治疗选择的方法越来越多地应用于临床试验，与改善反应率和生存率呈有利相关性。在弥漫性大 B 细胞淋巴瘤 (DLBCL) 患者中，疾病特征和结局可能差异很大，这突出表明通过识别敏感的预后特征对患者进行分类的重要性。基于细胞起源 (COO) 的不同 DLBCL 分子亚型的发现正在重新定义这种异质性癌症的预后和治疗。由于激活 B 细胞样 (ABC)-和生发中心 B 细胞样 (GCB)-DLBCL 亚型之间存在显著的分子和临床差异，因此 COO 识别为优化治疗选择提供了机会。广泛采用 COO 分类将极大地改善治疗和预后；然而，免疫组织化学技术之间的实验室一致性、成本和基因表达谱分析工具的可用性方面的限制，阻碍了 COO 在临床环境中的普遍整合。随着确定 COO 的先进方法在现实临床环境中的应用，针对特定亚型的治疗方法正在开发中。这里的重点是通过 COO 确定在 DLBCL 患者中应用精准医学来进行综述。
