Blood:Notch信号促进慢性淋巴细胞白血病发生发展

2020-12-21 MedSci原创 MedSci原创

NOTCH1基因功能获得性突变在慢性B淋巴细胞白血病(B-ALL)中常见,与病程进展加速和对化疗抵抗相关。然而,迄今为止,NOTCH1中这种恶性肿瘤发生发展中的特殊性作用仍未完全明确。

中心点:

IgH.TEμ CLL小鼠模型可如实再现人CLL的病理特征;

Notch信号促进CLL疾病的发生,促进细胞增殖和CLL病程进展。


NOTCH1基因功能获得性突变在慢性B淋巴细胞白血病(B-ALL)中常见,与病程进展加速和对化疗抵抗相关。然而,迄今为止,NOTCH1中这种恶性肿瘤发生发展中的特殊性作用仍未完全明确。

该研究旨在评估Notch信号缺失及其通路过度激活对可如实再现人CLL病理特征的CLL小鼠模型(IgH.TEm)的影响。

使用RBP-J条件性失活基因废除未成熟的造血或B细胞祖细胞中的经典Notch信号传导,可延迟CLL的诱导并降低了CLL小鼠的发病率。相反,过度激活Notch信号可增加发展成CLL的小鼠数量,且发病时间提前

对携带Notch功能获得性突变的和对照CLL细胞的基因表达及表观遗传特征进行对比分析发现,Notch信号直接间接调控细胞周期相关基因表达,导致体内携带Notch功能获得性突变的CLL细胞的增殖能力增强

总而言之,该研究结果表明,Notch信号可促进CLL的发生,并促进CLL细胞增殖和病程进展

原始出处:

Delphine Tardivon, et al. Notch Signaling Promotes Disease Initiation and Progression in Murine Chronic Lymphocytic Leukemia. Blood. December 18, 2020.

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  5. 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topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=30c82496029, createdName=1248b370m54暂无昵称, createdTime=Mon Dec 21 19:08:58 CST 2020, time=2020-12-21, status=1, ipAttribution=)]
    2020-12-27 chenxianglei

    notch突变引起CLl进展的机制仍需进一步探讨

    0

  6. 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  7. 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    2020-12-23 karmond
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    2020-12-23 ymljack
  9. 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    2020-12-21 1248b370m54暂无昵称

    学习了!

    0

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