BCL6公司
癌症研究
心理压抑
淋巴瘤
弥漫性大B细胞淋巴瘤
抑制因子
生物
组蛋白脱乙酰基酶
生发中心
基因
遗传学
B细胞
转录因子
组蛋白
免疫学
基因表达
抗体
作者
Samir Parekh,Gilbert G. Privé,Ari Melnick
标识
DOI:10.1080/10428190801895345
摘要
BCL6 is a transcriptional repressor often expressed constitutively in diffuse large B-cell lymphomas (DLBCL) due to mutations of its genomic locus. BCL6 mediates aberrant survival, proliferation, genomic instability and differentiation blockade in DLBCL cells. The biochemical study of BCL6 mediated gene repression has provided the basis for design of agents that inhibit BCL6 and kill lymphoma cells. The repressor activity of the BCL6 BTB domain is particularly well defined from the structural standpoint. Design of inhibitors targeting BCL6 BTB domain protein interaction surfaces appears to be an effective approach, which reactivates important BCL6 target genes and readily kills DLBCL cells. Targeting other domains of BCL6 or using histone deacetylase inhibitors to overcome BCL6 mediated repression may also be useful. Recent studies in DLBCL transcriptional signatures have revealed a subset of DLBCLs that are particularly dependent on BCL6 to maintain their survival and these patients could be candidates for clinical trials of BCL6 inhibitors.
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