PDF(Pubmed)
Abstract：
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.
摘要：
双表达淋巴瘤(DEL),以MYC和BCL-2高表达为特征，在目前的治疗后显示预后不良。HDAC抑制剂西达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。这里,通过结合抑制筛选和转录组学分析，我们发现B淋巴瘤细胞对西达胺的敏感性与MYC的表达水平呈正相关。Chidamide治疗可降低MYC蛋白水平并抑制MYC高表达的B淋巴瘤细胞MYC通路。西达本胺不敏感B淋巴瘤细胞中MYC的异位表达增加了其对西达本胺的反应。因此，我们提出将西达胺加入R-CHOP(CR-CHOP)可能对DEL有效，并对华西医院收治的185例DEL患者进行回顾性分析。80%的患者对CR-CHOP治疗有反应。在42个月的中位随访中，CR-CHOP可显著提高R-IPI≤2的DEL患者的生存率。共有35例患者在缓解期接受了自体干细胞移植（ASCT），并显示出更好的生存率趋势。将CR-CHOP与ASCT结合使用可获得最优异的PFS和OS。对于有反应的患者，与有或没有ASCT的R-CHOP样方案相比，CR-CHOP减少了复发，PFS更好。一起来看,我们的数据表明,西达胺抑制了B淋巴瘤的MYC通路,对治疗DEL有潜在疗效.
