Li Meng, Wang Xiaoli, He Wenjuan, Zhou Hao
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Med (Lausanne). 2025 May 14;12:1586552. doi: 10.3389/fmed.2025.1586552. eCollection 2025.
Acute myeloid leukemia (AML) exhibits a pronounced ability to develop drug resistance and undergo disease relapse. Recent research has noticed that resistance to treatments could substantially be attributed to drug-tolerant persister (DTP) cells, which are capable of surviving under therapeutic pressures. These are transient, reversibly dormant cells with the capability to act as a reservoir for disease relapse. DTP cells utilize diverse adaptive strategies to optimize the ecological niche, undergo metabolic reprogramming, and interact with microenvironment. The persister state of AML is established through transient cellular reprogramming, thus allowing cells to survive the initial phase of drug therapy and develop drug resistance. Our review explores the identification and phenotypic characteristics of AML DTP cells, as well as their clinical relevance. We summarize the mechanisms underlying the persistence of AML DTP cells and the molecular attributes that define the DTP state. We further address the current challenges and future prospects of DTP-targeting approaches. Understanding these features may provide critical insights into novel therapeutic strategies aimed at targeting AML DTP cells, especially in the new era of immunotherapy against AML.
急性髓系白血病（AML）具有显著的产生耐药性和疾病复发的能力。最近的研究发现，对治疗的耐药性在很大程度上可归因于耐药持久性细胞（DTP），这些细胞能够在治疗压力下存活。它们是短暂的、可逆性休眠的细胞，能够作为疾病复发的细胞库。DTP细胞利用多种适应性策略来优化生态位、进行代谢重编程并与微环境相互作用。AML的持久性状态是通过短暂的细胞重编程建立的，从而使细胞能够在药物治疗的初始阶段存活并产生耐药性。我们的综述探讨了AML DTP细胞的鉴定和表型特征，以及它们的临床相关性。我们总结了AML DTP细胞持续存在的潜在机制以及定义DTP状态的分子特征。我们还进一步阐述了靶向DTP方法当前面临的挑战和未来前景。了解这些特征可能为针对AML DTP细胞的新型治疗策略提供关键见解，尤其是在抗AML免疫治疗的新时代。
