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急性髓系白血病鞘脂代谢重塑及其靶向治疗研究进展

吴铨, 曾辉^*

南方医科大学附属广东省人民医院(广东省医学科学院)血液内科，广州 510080

摘要

鞘脂是一类兼具膜结构成分和信号调控功能的生物活性脂质，其代谢产物神经酰胺(ceramide, Cer)、鞘氨醇(sphingosine, Sph)和1-磷酸鞘氨醇(sphingosine-1-phosphate, S1P)在细胞增殖、凋亡、自噬、应激反应等生物学过程中发挥重要调控作用。在部分急性髓系白血病(acute myeloid leukemia, AML)模型中可观察到以Cer 稳态失衡为重要特征的鞘脂代谢重塑，这一过程与AML细胞存活、治疗耐药和疾病复发密切相关。本文围绕AML中鞘脂代谢重塑的关键环节，阐述其在AML细胞生存维持和药物耐受中的作用，并概述靶向鞘脂代谢关键节点的潜在治疗策略。

关键词： 急性髓系白血病; 鞘脂代谢; 神经酰胺; 1-磷酸鞘氨醇; 治疗耐药

Research progress on sphingolipid metabolic remodeling and targeted therapy in acute myeloid leukemia

WU Quan, ZENG Hui^*

Department of Hematology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China

Abstract

Sphingolipids are a class of bioactive lipids that serve as both structural components of cellular membranes and key regulators of signal transduction. Their metabolic derivatives, including ceramide (Cer), sphingosine (Sph), and sphingosine-1-phosphate (S1P), play important regulatory roles in diverse biological processes, such as cell proliferation, apoptosis, autophagy, and stress responses. In selected acute myeloid leukemia (AML) models, sphingolipid metabolic remodeling characterized by disrupted Cer homeostasis has been observed and is closely associated with AML cell survival, therapeutic resistance, and disease relapse. In this review, we focus on the key processes involved in sphingolipid metabolic remodeling in AML, discuss their roles in sustaining AML cell survival and mediating drug resistance, and summarize potential therapeutic strategies targeting critical nodes of sphingolipid metabolism.

Key words: acute myeloid leukemia; sphingolipid metabolism; ceramide; sphingosine-1-phosphate; therapeutic resistance

收稿日期：　　录用日期：

通讯作者：曾辉　　E-mail:

DOI: 10.13294/j.aps.2026.0085

引用本文：

吴铨, 曾辉. 急性髓系白血病鞘脂代谢重塑及其靶向治疗研究进展[J]. 生理学报 2026; 78 (4): 803-814.

WU Quan, ZENG Hui. Research progress on sphingolipid metabolic remodeling and targeted therapy in acute myeloid leukemia. Acta Physiol Sin 2026; 78 (4): 803-814 (in Chinese with English abstract).