细胞周期限制限制了DNA损伤,并维持了白血病干细胞的自我更新
Andrea Viale1, Francesca De Franco, Annette Orleth
1Department of Experimental Oncology at the IFOM-IEO Campus, European Institute of Oncology, IEO, 20141 Milan, Italy. andrea.viale@ifom-ieo-campus.it
Nature
|January 6, 2009
概括
白血病干细胞依赖细胞循环抑制剂p21进行自我更新. 抑制DNA修复可能提供一种新的策略来消除这些缓慢生长的癌症干细胞.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 血液学 血液学 血液学
背景情况:
- 罕见的干细胞驱动白血病的发展和自我更新.
- 维持白血病干细胞的分子机制尚不清楚.
- 白血病干细胞表现出扩大的自我更新能力.
研究的目的:
- 研究p21在白血病干细胞自我更新中的作用.
- 阐明白血病干细胞维护背后的分子机制.
- 确定针对白血病干细胞的潜在治疗策略.
主要方法:
- 使用了小鼠造血干细胞 (HSC).
- 诱导白血病相关瘤基因的表达.
- 分析了p21表达和DNA损伤反应.
- 评估细胞循环停止和DNA修复机制.
主要成果:
- p21表达对于白血病干细胞自我更新至关重要.
- 白血病瘤基因诱导DNA损伤,激活了p21依赖的反应.
- 激活的p21可以防止过度的DNA损伤和白血病干细胞的耗尽.
- 通过维持白血病干细胞的功能,p21起着致癌作用.
结论:
- p21对于维持白血病干细胞自我更新是不可或缺的.
- 准DNA修复机制可能是对抗白血病的有效策略.
- 了解p21的作用为消除白血病开辟了新的途径.
相关概念视频
Negative Regulator Molecules
32.1K
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
32.1K
DNA Damage can Stall the Cell Cycle
8.5K
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
8.5K
Replicative Cell Senescence
3.5K
Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds...
3.5K
Cancer Stem Cells and Tumor Maintenance
4.3K
Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
4.3K
DNA Damage Can Stall the Cell Cycle
2.4K
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
2.4K
Molecular Factors Affecting Cell Division
3.9K
Several external and internal factors influence the initiation and inhibition of cell division. For instance, the death of nearby cells or the release of human growth hormone (hGH) promotes cell division. In contrast, lack of hGH or crowding of cells can inhibit cell division.
Several proteins function as internal regulators to ensure each cell cycle stage is completed faithfully before proceeding to the next. Regulator molecules may act directly or influence the activity or production of other...
Several proteins function as internal regulators to ensure each cell cycle stage is completed faithfully before proceeding to the next. Regulator molecules may act directly or influence the activity or production of other...
3.9K


