在MLL重组白血病中对MLL退化途径的治疗向
Kaiwei Liang1, Andrew G Volk2, Jeffrey S Haug3
1Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, 320 E. Superior St., Chicago, IL 60611, USA; Stowers Institute for Medical Research, 1000 E. 50th St., Kansas City, MO 64110, USA.
Cell
|January 10, 2017
概括
UBE2O调节野生型MLL的稳定性,影响白血病的进展. 稳定野生型MLL蛋白为混合系白血病 (MLL) 和其他转位驱动的癌症提供了新的治疗策略.
科学领域:
- 分子生物学
- 癌症学
- 生物化学
背景情况:
- 涉及混合系白血病 (MLL) 基因的染色体转移与预后不佳的侵袭性白血病有关.
- 由这些转移产生的化学MLL蛋白比野生型MLL具有更高的稳定性,有助于白血病发生.
- 了解MLL蛋白稳定的调节机制对于开发有效的治疗方法至关重要.
研究的目的:
- 调查UBE2O对野生型MLL蛋白稳定性的作用.
- 探索针对MLL白血病中的MLL蛋白降解的治疗潜力.
- 阐明调制MLL稳定性如何影响MLL仿真体活动和瘤信号.
主要方法:
- 研究了UBE2O与野生类型MLL之间对互白素-1信号的反应.
- 评估了向野生型MLL降解对MLL白血病细胞增殖的影响.
- 分析了下游对MLL仿真基因和超延长复合物的影响.
- 在小鼠白血病模型中评估药理上抑制该途径的治疗效果.
主要成果:
- UBE2O被确定为野生型MLL稳定的关键调节剂,特别是在互白素-1信号下.
- 向野生型MLL降解显著阻碍了MLL白血病细胞的增殖.
- 这种干预降低了MLL仿真体的特定目标基因及其辅因子超延长复合体.
- 通过稳定野生型MLL,该途径的药理抑制改善了小鼠白血病模型的生存率和延迟进展.
结论:
- 稳定野生型MLL蛋白可以从目标基因中取代MLL仿真体,从而减少细胞对这些致癌驱动物的依赖.
- 调节MLL蛋白质的稳定性为侵袭性MLL白血病提供了一个有前途的治疗模式.
- 这种方法也可能适用于由染色体转移驱动的其他癌症.
相关概念视频
02:57Targeted Cancer Therapies
9.0K
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...
9.0K
02:50Combination Therapies and Personalized Medicine
6.3K
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...
6.3K
02:23Abnormal Proliferation
5.3K
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...
5.3K
02:38Mitogens and the Cell Cycle
8.2K
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
8.2K