[在淋巴瘤治疗中使用EZH抑制剂]
1Department of Hematology and Rheumatology, Kagoshima University.
概括
增强器的凝血同类 (EZH) 向在淋巴瘤中的基因表达. 通过恢复沉默的基因,EZH抑制为B细胞恶性瘤提供了一个有希望的治疗策略.
科学领域:
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 分子生物学分子生物学
- 在瘤学瘤学.
背景情况:
- 增强体同类 (EZH) 的增强剂,是多抑制复合体2 (PRC2) 的一个关键子单元,在通过H3K27甲基化对基因沉默起到关键作用.
- EZH与B细胞发育和恶性淋巴瘤的发病有关,包括毛囊淋巴瘤 (FL) 和扩散性大B细胞淋巴瘤 (DLBCL).
- 异常EZH2功能,包括功能获取突变和上调,在FL和DLBCL病例中的很大一部分中观察到.
研究的目的:
- 研究EZH在B细胞恶性瘤中的作用.
- 探索EZH抑制在淋巴瘤治疗中的治疗潜力.
- 了解EZH上调对成年T细胞白血病/淋巴瘤 (ATL) 基因抑制的影响.
主要方法:
- 在FL和DLBCL中分析EZH2突变和表达水平.
- 在ATL中评估H3K27三甲基化模式.
- 在临床前和临床环境中对EZH抑制剂的评估.
主要成果:
- 功能获取突变和EZH2的上调在FL和DLBCL中很普遍.
- EZH2和EZH1的上调导致全基因组的H3K27三甲基化,导致ATL中的大量基因抑制.
- 抑制EZH有效降低H3K27甲基化,并重新激活表观遗传沉默基因.
结论:
- 针对EZH的疗法,包括EZH2和双EZH1/2抑制剂,已获得临床批准用于治疗复发性/耐药性FL和ATL.
- 抑制EZH代表了淋巴瘤的新疗法,并正在对其他恶性瘤进行研究.
- 进一步开发针对EZH的治疗方法,单独或组合,对各种癌症具有显著的前景.
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