Shimada Kazuyuki
Department of Hematology and Oncology, Nagoya University Graduate School of Medicine.
Rinsho Ketsueki. 2017;58(10):2033-2042. doi: 10.11406/rinketsu.58.2033.
Diffuse large B-cell lymphoma (DLBCL) represents the most common subtype of non-Hodgkin lymphoma, accounting for 30%-40% of all types of malignant lymphoma. Importantly, two distinct molecular subtypes, germinal center B-cell (GCB) type and activated B-cell (ABC) type, arising from B lymphocyte differentiation based on the gene expression profiling opened doors to uncover molecular pathogenesis in DLBCL. Since 2010, next-generation sequencing analyses have been revealing the landscape of genetic mutations in DLBCL. Reportedly, GCB DLBCL is characterized by the accumulation of genetic abnormalities of epigenetic modifiers. Conversely, the hallmark of ABC DLBCL is the constitutive activation of the NKκB signaling pathway due to mutations in related genes. From recent prospective trials, conventional R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) regimen, which is the current standard regimen for DLBCL, has been acknowledged as a well-established regimen for DLBCL. Currently, the development of a plethora of drugs targeting the activated signaling pathway and immune microenvironments is ongoing. To overcome this intractable disease with the present treatment, the breakthroughs based on molecular pathogenesis are required.
弥漫性大B细胞淋巴瘤（DLBCL）是最常见的非霍奇金淋巴瘤亚型，占所有恶性淋巴瘤类型的30%-40%。重要的是，基于基因表达谱分析，从B淋巴细胞分化产生的两种不同分子亚型，即生发中心B细胞（GCB）型和活化B细胞（ABC）型，为揭示DLBCL的分子发病机制打开了大门。自2010年以来，下一代测序分析不断揭示DLBCL中的基因突变情况。据报道，GCB DLBCL的特征是表观遗传修饰因子的遗传异常积累。相反，ABC DLBCL的标志是由于相关基因突变导致NKκB信号通路的组成性激活。从最近的前瞻性试验来看，传统的R-CHOP（利妥昔单抗、环磷酰胺、多柔比星、长春新碱和泼尼松龙）方案，即目前DLBCL的标准方案，已被公认为是一种成熟的DLBCL治疗方案。目前，针对活化信号通路和免疫微环境的大量药物正在研发中。为了用目前的治疗方法攻克这种难治性疾病，需要基于分子发病机制取得突破。
