[MLL重组白血病的分子机制和治疗向]
1National Cancer Center Tsuruoka Metabolomics Laboratory.
概括
MLL基因重排驱动白血病,通过产生激活癌症驱动基因的融合蛋白来激活癌症. 准MLL-MENIN相互作用为白血病治疗提供了一个有前途的治疗策略.
科学领域:
- 分子生物学分子生物学
- 癌症遗传学 癌症遗传学
- 血液学 血液学 血液学
背景情况:
- MLL基因重组是恶性白血病的重要原因.
- 这些重组导致融合蛋白,构成性地激活HOXA9和MEIS1.1等关键瘤基因.
- 这种激活转化为造血原生细胞,驱动白血病发生.
研究的目的:
- 阐明MLL驱动型白血病发生的分子机制.
- 为了确定关键的蛋白质相互作用和参与MLL融合介导转化中的结构域.
- 探索针对MLL融合蛋白复合体的治疗策略.
主要方法:
- 相互作用组分析以确定相关的蛋白质.
- 在MLL融合蛋白的域映射.
- 蛋白质-DNA相互作用和表观遗传修饰的分析.
主要成果:
- MENIN被确定为与MLL合并相关的共同因素.
- 在MLL融合的MENIN结合动机和CXXC域对于白血病转化至关重要.
- 该MLL-MENIN-LEDGF复合体稳定地与具有特定基因素标记 (H3K36me2 / 3) 的CpG丰富促进体结合,使目标基因识别成为可能.
结论:
- MENIN,MLL融合和LEDGF蛋白质复合体的组合对于诱导白血病至关重要.
- 这种复杂的形成是药物介导抑制的可行目标.
- 干扰MENIN-MLL相互作用的治疗药物正在临床研究中,其中一些药物显示出有希望的结果.
相关概念视频
Targeted Cancer Therapies
7.8K
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...
7.8K
Combination Therapies and Personalized Medicine
5.1K
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...
5.1K
Treatment Resistant Cancers
3.4K
Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.4K
Mitogens and the Cell Cycle
6.8K
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...
6.8K
Abnormal Proliferation
4.6K
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...
4.6K
Transducer Mechanism: Enzyme-Linked Receptors
2.8K
Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Major types that are helpful drug targets include:
2.8K


