加压器
髓系白血病
癌症研究
自噬
突变
生物
基因组不稳定性
骨髓增生异常综合症
细胞生物学
抑制因子
遗传学
DNA损伤
细胞凋亡
免疫学
基因
DNA
转录因子
骨髓
作者
Jianan Chen,Jiacheng Jin,Juan Guo,Tao Ying,Fan-Huan Xu,Qi Liu,Li Xiao,Chunkang Chang,Lingyun Wu
标识
DOI:10.1016/j.biocel.2023.106480
摘要
The occurrence of autophagy dysregulation is vital in the development of myelodysplastic syndrome and its transformation to acute myeloid leukemia. However, the mechanisms are largely unknown. Here, we have investigated the mechanism of the bcl6 corepressor mutation in myelodysplastic syndrome development and its transformation to acute myeloid leukemia. We identified a novel pathway involving histone deacetylase 6 and forkhead box protein O1, which leads to autophagy defects following the bcl6 corepressor mutation. And this further causes apoptosis and cell cycle arrest. The bcl6 corepressor-mutation-repressed autophagy resulted in the accumulation of damaged mitochondria, DNA, and reactive oxygen species in myelodysplastic syndrome cells, which could then lead to genomic instability and spontaneous mutation. Our results suggest that the bcl6 corepressor inactivating mutations exert pro-carcinogenic effects through survival strike, which is only an intermediate process. These findings provide mechanistic insights into the role of the bcl6 corepressor gene in myelodysplastic syndrome.
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