由MLL-AF9启动的从承诺的原始细胞转化为白血病干细胞
Andrei V Krivtsov1, David Twomey, Zhaohui Feng
1Division of Hematology/Oncology, Children's Hospital, Boston, Massachusetts 02115, USA.
Nature
|July 25, 2006
概括
癌症干细胞,包括白血病干细胞 (LSC),可以在没有广泛的基因重编程的情况下从承诺的祖先产生. 针对他们的自我更新计划提供了一个潜在的治疗策略.
科学领域:
- 血液学 血液学 血液学
- 癌症生物学 癌症生物学
- 干细胞研究 干细胞研究
背景情况:
- 癌症干细胞驱动瘤的启动和维护,需要它们的根除以进行治疗疗法.
- 传统的治疗方法可以减少瘤的负担,但由于这些细胞的持久性,很少治愈.
- 了解癌症干细胞和正常组织干细胞之间的关系对于开发向疗法至关重要.
研究的目的:
- 调查白血病干细胞 (LSC) 是否必须与正常组织干细胞相似,或者是否可以来自已承诺的祖先.
- 定义癌症干细胞从正常祖先生成的过程.
主要方法:
- 从MLL-AF9诱导的白血病中隔离了LSC在已确定的粒细胞巨原体中.
- 白血病转移到二次接受者小鼠.
- 免疫类型定型和全球基因表达造型的LSC和正常的祖先.
主要成果:
- 在很少细胞的二次受体中,LSC可能会诱导白血病.
- 与正常的颗粒细胞-巨细胞祖先共享的免疫类型和全球基因表达.
- 通常在造血干细胞中发现的基因子集在LSC中被重新激活.
结论:
- 白血病干细胞可以在没有广泛的基因重编程的情况下从承诺的祖先中发展.
- 在这个过程中,特定于白血病的自我更新程序被激活.
- 针对这种异常的自我更新程序提供了一个潜在的治疗途径.
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