Autophagy ( IF 14.6 ) Pub Date : 2022-03-01 , DOI: 10.1080/15548627.2022.2041152 Angela Ianniciello 1 , G Vignir Helgason 1
ABSTRACT
Minimal residual disease (MRD) refers to a low number of cells that persist anti-cancer treatment and is the major cause of relapse in solid cancers and leukemias. In chronic myeloid leukemia (CML), a paradigm for stem cell-driven cancer, MRD is maintained by tyrosine kinase inhibitor (TKI)-insensitive leukemic stem cells (LSCs), which may rely on fundamental metabolic processes to resist drug treatment. Macroautophagy/autophagy is a cytoprotective process that has been highlighted as critical for sustaining LSC survival during TKI treatment in robust experimental models of CML. Our recent study shows that the autophagy-initiating kinase ULK1 is required for maintaining energy and redox balance in CML LSCs. Pharmacological inhibition of ULK1 results in stress-induced differentiation of LSCs, rendering them sensitive to TKI treatment, uncovering a promising strategy for selective eradication of LSCs in CML patients.
Abbreviations CML: chronic myeloid leukemia; LSC: leukemic stem cell; MAPK: mitogen-activated protein kinase; MRD: minimal residual disease; TKI: tyrosine kinase inhibitor
中文翻译:
![](https://scdn.x-mol.com/jcss/images/paperTranslation.png)
靶向癌症干细胞中的 ULK1:慢性粒细胞白血病的见解
抽象的
微小残留病(MRD)是指持续抗癌治疗的细胞数量较少,是实体癌和白血病复发的主要原因。在慢性粒细胞白血病 (CML)(干细胞驱动癌症的一种范例)中,MRD 由酪氨酸激酶抑制剂 (TKI) 不敏感的白血病干细胞 (LSC) 维持,这些细胞可能依赖基本代谢过程来抵抗药物治疗。巨自噬/自噬是一种细胞保护过程,在稳健的 CML 实验模型中,TKI 治疗期间,它对于维持 LSC 存活至关重要。我们最近的研究表明,自噬启动激酶 ULK1 是维持 CML LSC 能量和氧化还原平衡所必需的。 ULK1 的药理抑制会导致应激诱导的 LSC 分化,使它们对 TKI 治疗敏感,从而揭示了选择性根除 CML 患者 LSC 的有前途的策略。
缩写CML:慢性粒细胞白血病; LSC:白血病干细胞; MAPK:丝裂原激活蛋白激酶; MRD:微小残留病; TKI:酪氨酸激酶抑制剂