Hematology Department, The Second Affiliated Hospital of Soochow University, Suzhou, PR China.
Pathology Department, The Second Affiliated Hospital of Soochow University, Suzhou, PR China.
Leuk Lymphoma. 2022 Dec;63(14):3370-3377. doi: 10.1080/10428194.2022.2131411. Epub 2022 Oct 14.
Diffuse large B-cell lymphomas (DLBCLs) are phenotypically and genetically heterogeneous. Two main subgroups of DLBCL include germinal center B-cell-like (GCB) and activated B-cell-like (ABC). Molecular profiling can further classify DLBCL into four subtypes: MCD (both CD79B and MYD88 L265P), BN2 (NOTCH2 mutation or BCL6 fusion), N1 (NOTCH1 mutation), or EZB (EZH2 mutation or BCL2 fusion). EZH2 inhibitors were recommended for patients with the EZB subtype of DLBCLs; however, little is known about the therapeutic mechanisms. Our results showed that DZNep arrested G1/S phase of GCB-DLBCL cells and inhibited the cell proliferation through upregulation of p16 by demethylating its promoter. These results suggest that DZNep may have potential as a novel therapeutic agent for DFLBL therapy. This agent may serve as a novel molecular agent to be applied to GCB DLBCL.
弥漫性大 B 细胞淋巴瘤（DLBCLs）在表型和遗传上具有异质性。DLBCL 有两个主要亚群，包括生发中心 B 细胞样（GCB）和激活 B 细胞样（ABC）。分子谱分析可以进一步将 DLBCL 分为四个亚型：MCD（CD79B 和 MYD88 L265P 均阳性）、BN2（NOTCH2 突变或 BCL6 融合）、N1（NOTCH1 突变）或 EZB（EZH2 突变或 BCL2 融合）。推荐 EZH2 抑制剂用于治疗 EZB 亚型的 DLBCLs 患者；然而，对于其治疗机制知之甚少。我们的研究结果表明，DZNep 通过去甲基化其启动子使 p16 上调，从而阻滞 GCB-DLBCL 细胞的 G1/S 期并抑制细胞增殖。这些结果表明，DZNep 可能具有作为弥漫性大 B 细胞淋巴瘤新的治疗药物的潜力。该药物可能作为一种新的分子药物应用于 GCB-DLBCL。
