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解析急性髓系白血病治疗中的脂质代谢

Unraveling lipid metabolism for acute myeloid leukemia therapy.

作者信息

O'Brien Cristiana, Jones Courtney L

机构信息

Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.

Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.

出版信息

Curr Opin Hematol. 2025 Mar 1;32(2):77-86. doi: 10.1097/MOH.0000000000000853. Epub 2024 Nov 25.

Abstract

PURPOSE OF REVIEW

The aim of this review is to highlight the importance of lipids' intricate and interwoven role in mediating diverse acute myeloid leukemia (AML) processes, as well as potentially novel lipid targeting strategies. This review will focus on new studies of lipid metabolism in human leukemia, particularly highlighting work in leukemic stem cells (LSCs), where lipids were assessed directly as a metabolite.

RECENT FINDINGS

Lipid metabolism is essential to support LSC function and AML survival through diverse mechanisms including supporting energy production, membrane composition, signaling pathways, and ferroptosis. Recent work has highlighted the role of lipid rewiring in metabolic plasticity which can underlie therapy response, the impact of cellular and genetic heterogeneity in AML on lipid metabolism, and the discovery of noncanonical roles of lipid related proteins in AML.

SUMMARY

Recent findings around lipid metabolism clearly demonstrates their importance to our understanding and therapeutic targeting of AML. We have only begun to unravel the regulation and utilization of lipids in this disease. Further, understanding the layered dynamics of lipid homeostasis could provide novel opportunities to target lipid metabolism in AML and LSCs with the potential of improving outcomes for patients with AML.

摘要

综述目的

本综述旨在强调脂质在介导多种急性髓系白血病(AML)过程中复杂且相互交织的作用的重要性,以及潜在的新型脂质靶向策略。本综述将聚焦于人类白血病中脂质代谢的新研究,尤其突出对白血病干细胞(LSC)的研究工作,其中脂质被直接评估为一种代谢物。

最新发现

脂质代谢通过多种机制对支持LSC功能和AML存活至关重要,这些机制包括支持能量产生、膜组成、信号通路和铁死亡。近期研究突出了脂质重塑在代谢可塑性中的作用,这可能是治疗反应的基础,AML中细胞和基因异质性对脂质代谢的影响,以及脂质相关蛋白在AML中的非经典作用的发现。

总结

近期关于脂质代谢的发现清楚地表明了它们对我们理解和治疗AML的重要性。我们才刚刚开始揭示脂质在这种疾病中的调节和利用情况。此外,了解脂质稳态的分层动态变化可为靶向AML和LSC中的脂质代谢提供新机会,有可能改善AML患者的治疗结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/371b/11789610/bcfd48150b8d/cohem-32-77-g001.jpg

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