BCL6使Ph+急性淋巴细胞白血病细胞能够在BCR-ABL1激酶抑制下生存
Cihangir Duy1, Christian Hurtz, Seyedmehdi Shojaee
1Department of Laboratory Medicine, University of California San Francisco, San Francisco, California 94143, USA.
Nature
|May 20, 2011
概括
氨酸激酶抑制剂 (TKIs) 可能无法消除白血病发起细胞,导致复发. 向BCL6通过抑制保护性反信号来克服这种药物耐药性,消除了耐药性白血病亚克隆.
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:
- 氨酸激酶抑制剂 (TKI) 是BCR-ABL1阳性白血病的标准治疗方法.
- 目前的TKI往往无法根除白血病发起细胞 (LIC),导致疾病复发.
研究的目的:
- 研究白血病中TKI耐药性的新机制.
- 确定克服耐药性和根除LICs的治疗目标.
主要方法:
- 对耐药白血病细胞信号通路的分析.
- 在TKI阻力中确定关键监管者.
- 在临床前模型中对已识别的耐药性途径进行有针对性的抑制.
主要成果:
- 发现了一种新的药物耐药性机制,涉及白血病细胞中保护性反信号.
- 确定了BCL6作为这种抗性途径的中心媒介.
- 证明BCL6抑制消除了耐药和白血病发起子克隆.
结论:
- 准BCL6是克服白血病中TKI耐药性的有希望的策略.
- 抑制BCL6可以消除持久性白血病发起细胞,防止复发.
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