Notch-Hes信号通路异常与急性白血病

Abnormal Notch-Hes Signaling Pathways and Acute Leukemia——Review

Notch信号的异常活化与急性白血病的关系密切。Notch信号通路的核心组件包括Notch受体、Notch配体、CSLDNA结合蛋白、下游靶基因等效应分子等4部分。任何影响配体、受体、信号转导分子及效应分子的因素都会对Notch信号通路的传递产生影响。基于异常Notch信号在急性白血病中的重要作用,目前已经开发出了多种针对Notch上游信号的靶向药物,但是由于Notch信号的复杂性、多效性,现有针对Notch上游信号的靶向药物毒副作用较多。Hes基因家族是Notch信号中一个非常重要的靶基因,并且与白血病发生之间的关系密切。本文简述了该研究领域的新进展,期望Hes蛋白或基因的深入研究能为研发新一代靶向药物提供参考。

The abnormal activation of Notch signaling is closely related to the development of acute leukemia（AL）.The core elements of the Notch signaling system include Notch receptors,Notch ligands,CSL DNA- binding proteins,and effectors like target genes.Any factors,which affect ligands,receptors,signal transducers and effectors,can influence the signal transduction of Notch signaling greatly.Based on the role of Notch signaling in AL,several targeted drugs against Notch upstream signaling have been developed.However,due to the complexity and pleiotropic effects of Notch upstream signaling,these targeted drugs display strong side effects.Thus,Hes（Hairy Enhancer of Split） factors as a primary Notch effector,also play an important role in the pathogenesis of AL.This review summarizes recent progresses on Notch-Hes signaling in AL,hopping to provide references for further excavation of the Notch-Hes signaling,and lay foundations for developing the next generation of targeted drugs.