Abstract:
Regulation of the fate of hematopoietic stem cells (HSCs), including silencing, self-renewal or differentiation into blood line cells, is crucial to maintain the homeostasis of the human blood system and prevent leukemia. Notch1, a key receptor in the Notch signaling pathway, plays an important regulatory role in these properties of HSCs, particularly in the maintenance of the stemness of HSCs. In recent decades, the ubiquitination modification of Notch1 has been gradually revealed, and also demonstrated to affect the proliferation and differentiation of HSCs. Therefore, a detailed elucidation of Notch1 and its ubiquitination modification may help to improve understanding of the maintenance of HSC properties and the pathogenesis of leukemia. In addition, it may aid in identifying potential therapeutic targets for specific leukemias and provide potential prognostic indicators for HSC transplantation (HSCT). In the present review, the association between Notch1 and HSCs and the link between the ubiquitination modification of Notch1 and HSCs were described. In addition, the association between abnormal HSCs mediated by Notch1 or ubiquitinated Notch1and T-cell acute lymphoblastic leukemia (T-ALL) was also examined, which provides a promising direction for clinical application.
摘要:
造血干细胞(HSC)命运的调节,包括沉默,自我更新或分化为血细胞,对于维持人体血液系统的稳态和预防白血病至关重要。Notch1是Notch信号通路的关键受体,在HSC的这些特性中起着重要的调节作用,特别是在维持HSC的干性方面。近几十年来,Notch1的泛素化修饰已经逐渐显现出来,并证实影响HSCs的增殖和分化。因此,详细阐明Notch1及其泛素化修饰可能有助于提高对HSC特性维持和白血病发病机制的认识.此外,它可能有助于确定特定白血病的潜在治疗靶点,并为HSC移植(HSCT)提供潜在的预后指标.在本次审查中,描述了Notch1与HSC之间的关联以及Notch1的泛素化修饰与HSC之间的联系。此外,还检查了Notch1或泛素化Notch1介导的异常HSC与T细胞急性淋巴细胞白血病(T-ALL)之间的关联,为临床应用提供了有希望的方向。