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急性髓系白血病中线粒体相关潜在治疗靶点研究新进展

韩璐^1,2, 刘莉^1,2, 刘静^1,2,*

¹中南大学生命科学学院，长沙 41001；²中南大学血液学基础与应用湖南省重点实验室，长沙 410078

摘要

急性髓系白血病(acute myeloid leukemia, AML)是最常见的白血病类型之一，具有恶性程度高和进展迅速的特点，导致其5年生存率不足30%。同时，随着年龄的增长，AML的发病率和死亡率均呈上升趋势。在过去的几十年里，AML的治疗进展相对缓慢。传统的治疗方法包括化疗和造血干细胞移植，但这些治疗方法有明显的局限性，包括但不限于出现贫血、感染等治疗毒性问题，以及化疗耐药等。近年来，AML机制研究的不断深入使靶向治疗成为新选择。代谢重编程是癌症的重要特征之一，线粒体功能异常在多种癌症中已被广泛研究，AML细胞线粒体功能普遍异常，并与AML发生、发展密切相关。AML细胞与正常造血细胞在能量代谢、自噬、凋亡等方面存在显著差异。线粒体是细胞能量代谢的核心，线粒体自噬和线粒体凋亡途径也影响AML细胞的存活和疾病进展。因此，抑制与线粒体功能相关的通路对于治疗AML具有显著的潜力。本综述将探讨近年来针对线粒体功能紊乱在AML细胞存活中的作用、线粒体中潜在治疗靶点以及相关靶向药物的研究进展，旨在为AML靶向治疗的发展提供思路。

关键词： 急性髓系白血病; 线粒体; 氧化磷酸化; 代谢; 治疗靶点

Recent advances in the study of potential mitochondria-related therapeutic targets in acute myeloid leukemia

HAN Lu^1,2, LIU Li^1,2, LIU Jing^1,2,*

¹School of Life Sciences, Central South University, Changsha 410013, China；²Key Laboratory of Basic and Applied Hematology in Hunan Province, Central South University, Changsha 410078, China

Abstract

Acute myeloid leukemia (AML), one of the most common types of leukemia, is characterized by its high malignancy and rapid progression with a 5-year survival rate of less than 30%. The incidence and mortality rates of AML are increasing with age. Over the past few decades, progress in AML treatment has been relatively slow. While traditional approaches such as chemotherapy and hematopoietic stem cell transplantation have significant limitations including treatment toxicity and chemotherapy resistance, recent advancements in the in-depth study of AML mechanisms have made targeted therapy a new option for AML treatment. Metabolic reprogramming is one of the key features of cancer, and mitochondrial dysfunction has been widely studied in various cancers. Mitochondrial dysfunction is prevalent in AML cells and closely associated with the development of AML. The AML cells exhibit significant differences from normal hematopoietic cells in energy metabolism, autophagy, apoptosis, and other aspects. Given that mitochondria are at the core of cellular energy metabolism, inhibiting pathways related to mitochondrial function holds significant potential for AML treatment. This review aims to explore recent advances on the role of mitochondrial dysfunction in AML cell survival, potential therapeutic targets in mitochondria, and related targeted drugs, aiming to provide ideas for the development of targeted therapies for AML.

Key words: acute myeloid leukemia; mitochondria; oxidative phosphorylation; metabolism; therapeutic targets

收稿日期：　　录用日期：

通讯作者：刘静　　E-mail:

DOI: 10.13294/j.aps.2024.0058

引用本文：

韩璐, 刘莉, 刘静. 急性髓系白血病中线粒体相关潜在治疗靶点研究新进展[J]. 生理学报 2024; 76 (4): 605-621.

HAN Lu, LIU Li, LIU Jing. Recent advances in the study of potential mitochondria-related therapeutic targets in acute myeloid leukemia. Acta Physiol Sin 2024; 76 (4): 605-621 (in Chinese with English abstract).