通过打破白血病干细胞休眠来靶向它们。
Targeting leukemic stem cells by breaking their dormancy.
机构信息
HI-STEM (Heidelberg Institute for Stem Cell Technology and Experimental Medicine), Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg, Germany.
出版信息
Mol Oncol. 2010 Oct;4(5):443-50. doi: 10.1016/j.molonc.2010.06.001. Epub 2010 Jun 9.
Abstract
Transient or long-term quiescence, the latter referred to as dormancy are fundamental features of at least some adult stem cells. The status of dormancy is likely a critical mechanism for the observed resistance of normal HSCs and leukemic stem cells (LSCs) to anti-proliferative chemotherapy. Recent studies have revealed cytokines such as Interferon-alpha (IFNα) and G-CSF as well as arsenic trioxide (As(2)O(3)) to be efficient agents for promoting cycling of dormant HSCs and LSCs. Most interestingly, such cell cycle activated stem cells become exquisitely sensitive to killing by different chemotherapeutic agents, suggesting that dormant LSCs in patients may be targeted by a sequential two-step protocol involving an initial activation by IFNα, G-CSF or As(2)O(3), followed by targeted chemotherapy.
摘要
短暂或长期的静止，后者被称为休眠，是至少一些成人干细胞的基本特征。休眠状态可能是观察到正常造血干细胞和白血病干细胞（LSCs）对抗增殖化疗具有抗性的关键机制。最近的研究表明，干扰素-α（IFNα）和 G-CSF 等细胞因子以及三氧化二砷（As（2）O（3））是促进休眠 HSCs 和 LSCs 循环的有效药物。最有趣的是，这种细胞周期激活的干细胞对不同的化疗药物变得非常敏感，这表明患者体内的休眠 LSCs 可能是通过一个两步顺序方案来靶向，该方案包括先用 IFNα、G-CSF 或 As（2）O（3）进行初始激活，然后进行靶向化疗。
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