University of Rochester School of Medicine, Wilmot Cancer Center, 601 Elmwood Avenue, Rochester, NY 14642, USA.
Best Pract Res Clin Haematol. 2012 Dec;25(4):415-8. doi: 10.1016/j.beha.2012.10.003. Epub 2012 Oct 23.
There are a number of approaches for selective targeting of leukemic stem cells (LSCs). These include targeting stem-cell properties, such as self-renewal, inducing cycling of quiescent LSCs to sensitize them to conventional agents, employing or inducing immune-based mechanisms, and targeting tumor-specific physiology. Agents such as parthenolide inhibit the ability of leukemic stem cells to respond to oxidative stress and make leukemic stem cells and bulk leukemic cells susceptible to cell death, while normal stem cells remain relatively unharmed by these agents. The major mechanism of action of these small molecules appears to revolve around the aberrant glutathione metabolism pathway found in leukemic cells.
有许多方法可用于选择性靶向白血病干细胞 (LSCs)。这些方法包括针对干细胞特性，如自我更新，诱导静止 LSCs 循环以使其对常规药物敏感，利用或诱导免疫机制，以及针对肿瘤特异性生理。例如，小白菊内酯可抑制白血病干细胞应对氧化应激的能力，使白血病干细胞和白血病细胞对细胞死亡敏感，而正常干细胞相对不受这些药物的影响。这些小分子的主要作用机制似乎围绕着白血病细胞中异常的谷胱甘肽代谢途径。
