作为T细胞白血病中中枢神经系统透的重要调节者,CCR7信号传递
Silvia Buonamici1, Thomas Trimarchi, Maria Grazia Ruocco
1Department of Pathology and New York University Cancer Institute, New York 10016, USA.
Nature
|June 19, 2009
概括
化基因受体CCR7对于T细胞急性淋巴细胞白血病 (T-ALL) 细胞进入中枢神经系统 (CNS) 是必不可少的. 向CCR7可能会减少T-ALL患者中枢神经系统并发症.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- T细胞急性淋巴细胞白血病 (T-ALL) 是一种严重的儿童癌症,具有中枢神经系统 (CNS) 复发的高风险.
- 目前的T-ALL治疗包括内辐射和内化疗,导致严重的长期副作用.
- 在T-ALL中,白血病细胞透到中枢神经系统的机制尚不清楚.
研究的目的:
- 确定驱动白血病T细胞透到T-ALL中枢神经系统的关键分子机制.
- 调查中枢神经系统中基因受体CCR7在T-ALL细胞向中枢神经系统中的作用.
- 探索潜在的治疗策略,以防止中枢神经系统参与T-ALL.
主要方法:
- 使用T-ALL动物模型和基因表达概况.
- 分析了CCR7及其配体CCL19.9的表达.
- 研究了沉默CCR7或CCL19对中枢神经系统透的影响.
- 研究了人类T-ALL细胞中枢神经系统针对小鼠模型中CCR7表达的依赖性.
主要成果:
- 化学因受体CCR7被确定为T-ALL细胞中枢神经系统向的关键粘附信号.
- CCR7基因表达受Notch1瘤基因的调节,并且存在于具有Notch1突变的人类T-ALL中.
- 在T-ALL动物模型中,抑制CCR7或CCL19显著抑制中枢神经系统透.
- 在小鼠中,人类T-ALL细胞的中枢神经系统定位取决于CCR7的表达.
结论:
- CCR7-CCL19相互作用是T-ALL细胞进入中枢神经系统的关键"入口"信号.
- 针对这种化学因受体通路提供了一个潜在的策略,以减少中枢神经系统参与T-ALL.
- 抑制中枢神经系统透可能使中枢神经系统向治疗的强度降低,从而减轻与治疗相关的毒性.
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