对于AML中白血病干细胞的发展,Wnt/β-catenin通路是必要的
Yingzi Wang1, Andrei V Krivtsov, Amit U Sinha
1Division of Hematology/Oncology, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
概括
准Wnt/β-catenin通路可能为急性髓性白血病 (AML) 提供一种新的治疗策略. 这一途径对于白血病干细胞 (LSCs) 的自我更新至关重要,这些干细胞驱动AML的维持.
科学领域:
- 血液学 血液学 血液学
- 在瘤学瘤学.
- 分子生物学分子生物学
背景情况:
- 白血病干细胞 (LSCs) 驱动急性骨髓性白血病 (AML) 的持续性和复发.
- 识别控制LSC自我更新的信号通路对于开发向疗法至关重要.
研究的目的:
- 研究Wnt/β-catenin信号通路在LSC自我更新中的作用.
- 确定这种途径是否对于AML小鼠模型中的LSC维护至关重要.
主要方法:
- 使用由瘤基因 (Hoxa9/Meis1a) 或融合瘤蛋白 (MLL-AF9) 诱导的AML小鼠模型.
- 检查了Wnt/β-catenin信号的要求,用于从血造干细胞 (HSC) 和花细胞-巨细胞 (GMP) 的血造干细胞自我更新.
主要成果:
- Wnt/β-catenin信号通路对于LSCs的自我更新至关重要.
- 这一要求在来自HSC和GMP的LSC中得到了遵守.
- 在癌基因诱导的转化后,Wnt/β-catenin信号在原生细胞中被重新激活.
结论:
- 在AML中,Wnt/β-catenin信号传递是LSC自我更新的关键驱动因素.
- 对于原始细胞的瘤基因诱导转化,需要重新激活β-catenin信号传递.
- 准Wnt/β-catenin通路为AML提供了一个潜在的新疗法策略.
相关概念视频
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Canonical Wnt Signaling Pathway
The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which results in tumor...
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Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
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Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
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