SMARCA5重新编程AKR1B1介导的果糖代谢,以控制白血病发生
Peng-Cheng Yu1, Dan Hou2, Binhe Chang2
1CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China; Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Developmental cell
|May 22, 2024
概括
白血病涉及改变的染色质可访问性,由SMARCA5.5驱动. 这种蛋白激活AKR1B1,通过重编程果糖代谢来促进癌症,提供新的治疗点.
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.
- 癌症生物学 癌症生物学
- 分子瘤学分子瘤学
背景情况:
- 白血病在染色质可访问性方面表现出显著的变化,这是一个表观遗传的标志.
- 在白血病中这些染色质改变的根本原因仍然在很大程度上是未知的.
研究的目的:
- 确定负责白血病中异常染色质可访问性的分子机制.
- 阐明已识别的因素在白血病发生中的作用,并探索潜在的治疗策略.
主要方法:
- 染色体免疫沉测序 (ChIP-seq) 用于评估染色体的可访问性.
- RNA测序 (RNA-seq) 用于分析基因表达.
- 生物化学测试以确定蛋白质相互作用.
- 在体内和体内白血病模型用于治疗评估.
主要成果:
- SMARCA5,模仿开关 (ISWI) 综合体的核心ATPase,被确定为白血病细胞中异常染色质可访问性的关键驱动因素.
- SMARCA5维持了这种异常的可访问性,并通过通过DDX5和SP1的招募来激活AKR1B1转录来促进白血病发生.
- 升高的AKR1B1水平与白血病患者的预后不佳相关,并通过果糖代谢重编程驱动白血病发生.
- 药理上抑制AKR1B1在临床前白血病模型和患者衍生细胞中显示出显著的治疗疗效.
结论:
- 由SMARCA5调解的异常染色体重塑对于白血病发生至关重要.
- SMARCA5诱导的AKR1B1激活和随后的果糖代谢重编程代表了白血病的新奇机制.
- 抑制AKR1B1为白血病治疗提供了一个有前途的治疗途径.
相关概念视频
02:50Combination Therapies and Personalized Medicine
4.9K
Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
4.9K
02:23Abnormal Proliferation
4.5K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.5K
02:57Targeted Cancer Therapies
7.6K
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
There are several types of targeted therapies against...
7.6K