Blood:CK1δ/ε抑制剂,PF-670462,治疗慢性淋巴细胞白血病的效果。

2018-01-15 MedSci MedSci原创

中心点:酪蛋白激酶1(CK1)抑制可显着阻滞CLL细胞的微环境互作。CK1抑制,可延缓Eμ-TCL1小鼠模型的CLL样疾病的进展。摘要:酪蛋白激酶(CK)1δ/ε是非经典Wnt信号通路的关键组成成分,既往研究已证实其可促进慢性淋巴白血病(CLL)的病程进展。现研究人员对CK1δ/ε抑制对原发性CLL细胞的影响进行全面的研究,并用两种Eμ-TCL1诱导的白血病小鼠模型系统分析其治疗潜能。研究人员证实

中心点:

酪蛋白激酶1(CK1)抑制可显着阻滞CLL细胞的微环境互作。

CK1抑制,可延缓Eμ-TCL1小鼠模型的CLL样疾病的进展。

摘要:

酪蛋白激酶(CK)1δ/ε是非经典Wnt信号通路的关键组成成分,既往研究已证实其可促进慢性淋巴白血病(CLL)的病程进展。现研究人员对CK1δ/ε抑制对原发性CLL细胞的影响进行全面的研究,并用两种Eμ-TCL1诱导的白血病小鼠模型系统分析其治疗潜能。

研究人员证实CK1δ/ε抑制剂PF-670462可显著阻滞CLL所有主要亚型的原发性CLL细胞的微环境互作(趋药性、侵袭性以及与基质细胞的交流)。在小鼠模型中,CK1抑制可延缓白血病细胞在外周血和脾脏中的累积,并防止贫血的发生。因此,PF-670462治疗可显著延长总体存活期。重要的是,CK1抑制与BCR抑制剂(如依鲁替尼)在活体内具有协同作用,可显著提高依鲁替尼的治疗效果。用PF-670462联合依鲁替尼治疗小鼠,白血病病程进展极为缓慢,存活期较单用依鲁替尼明显延长。

总而言之,CK1δ/ε抑制剂PF-670462的预临床试验证明CK1或许可作为CLL的新的治疗靶点,与BCR抑制剂协同作用。本研究为靶向CK1作基于B细胞受体信号和抗凋亡信号(BCL2)抑制的治疗方案替代或补充治疗提供实验支持。

原始出处:

Pavlina Janpvska, et al. Casein Kinase 1 is a Therapeutic Target in Chronic Lymphocytic Leukemia. Blood  2018  :blood-2017-05-786947;  doi: https://doi.org/10.1182/blood-2017-05-786947

本文系梅斯医学(MedSci)原创编译整理,转载需授权!

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    2018-08-03 jklm09
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    2018-01-15 1e0e5697m83(暂无匿称)

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