西达本胺可抑制 MYC 表达，并可能提高双表达淋巴瘤患者的生存率。
Chidamide represses MYC expression and might improve survival for patients with double expressor lymphoma.
发表日期：2024
作者：
Pengpeng Liu, Xiaohang Hang, Jianjun Li, Lei Zhao, Weiping Liu, Jie Ji, Yu Wu, Xudong Wan, Xiao Shuai, Yong Guo, Bing Xiang, Jiazhuo Liu, Jie Huang, Zhigang Liu, Li Hou, Chong Chen, Yu Liu, Ting Liu
来源：
Epigenetics & Chromatin
摘要：
双表达细胞淋巴瘤 (DEL) 的特点是 MYC 和 BCL-2 高表达，目前治疗后预后较差。 HDAC抑制剂西达本胺已被批准用于治疗T细胞淋巴瘤，但其对B细胞淋巴瘤的疗效尚不清楚。在这里，通过结合抑制筛选和转录组分析，我们发现B淋巴瘤细胞对西达本胺的敏感性与MYC的表达水平呈正相关。西达本胺治疗可降低 MYC 蛋白水平并抑制高 MYC 表达的 B 淋巴瘤细胞中的 MYC 通路。对西达本胺不敏感的 B 淋巴瘤细胞中 MYC 的异位表达增加了它们对西达本胺的反应。因此，我们提出在R-CHOP（CR-CHOP）中添加西达本胺可能对DEL有效，并回顾性分析了华西医院治疗的185例DEL患者。 80% 的患者对 CR-CHOP 治疗有反应。在中位随访 42 个月中，CR-CHOP 显着提高了 R-IPI ≤ 2 的 DEL 患者的生存率。共有 35 名患者在缓解后接受了自体干细胞移植 (ASCT)，并表现出了更好的生存趋势。 CR-CHOP 与 ASCT 相结合可实现最优异的 PFS 和 OS。对于有缓解的患者，CR-CHOP 减少了复发，并且比 R-CHOP 样方案（无论是否有 ASCT）都具有更好的 PFS。总而言之，我们的数据表明西达本胺抑制 B 淋巴瘤中的 MYC 通路，并且可能有效治疗 DEL。AJCR 版权所有 © 2024。
Double expressor lymphoma (DEL), characterized by high expressions of both MYC and BCL-2, displays poor prognosis after current therapies. The HDAC inhibitor chidamide has been approved for treatment of T cell lymphoma, but its efficacy on B cell lymphoma is unclear. Here, by combining inhibition screening and transcriptomic analyses, we found that the sensitivity of B lymphoma cells to chidamide was positively correlated with the expression levels of MYC. Chidamide treatment reduced MYC protein levels and repressed MYC pathway in B lymphoma cells with high MYC expressions. Ectopic expression of MYC in chidamide-insensitive B lymphoma cells increased their response to chidamide. Thus, we proposed that adding chidamide into R-CHOP (CR-CHOP) might be effective for DEL, and retrospectively analyzed 185 DEL patients treated in West China Hospital. 80% of patients showed response to CR-CHOP treatment. In the median follow-up of 42 months, CR-CHOP significantly improve the survival for DEL patients with R-IPI ≤2. Totally 35 patients underwent autologous stem cell transplantation (ASCT) in remission and demonstrated a trend for better survival. Combining CR-CHOP with ASCT resulted in the most superior PFS and OS above all. For response patients, CR-CHOP reduced relapse with better PFS than R-CHOP-like regimens with or without ASCT. Taken together, our data indicated that chidamide repressed the MYC pathway in B lymphoma and is potentially efficacious to treat DEL.AJCR Copyright © 2024.