Unraveling lipid metabolism for acute myeloid leukemia therapy.

IF 3.1 3区医学 Q2 HEMATOLOGY Current Opinion in Hematology Pub Date : 2024-11-19 DOI:10.1097/MOH.0000000000000853

Cristiana O'Brien, Courtney L Jones

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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.

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揭示急性髓性白血病治疗中的脂质代谢。

综述的目的：本综述旨在强调脂质在介导各种急性髓性白血病（AML）过程中错综复杂、相互交织的重要作用，以及潜在的新型脂质靶向策略。本综述将重点关注人类白血病中脂质代谢的新研究，尤其是在白血病干细胞（LSCs）中的研究，其中脂质作为一种代谢物被直接评估：脂质代谢对支持造血干细胞的功能和急性髓细胞性白血病的存活至关重要，其作用机制多种多样，包括支持能量生产、膜组成、信号通路和铁变态反应。最近的研究强调了脂质重构在代谢可塑性中的作用，这可能是治疗反应的基础，AML 中细胞和遗传异质性对脂质代谢的影响，以及发现脂质相关蛋白在 AML 中的非经典作用：围绕脂质代谢的最新研究成果清楚地表明，脂质代谢对我们了解和治疗急性髓细胞性白血病具有重要意义。我们才刚刚开始揭示脂质在这种疾病中的调节和利用。此外，了解脂质稳态的分层动态可为针对急性髓细胞性白血病和造血干细胞的脂质代谢提供新的机会，从而改善急性髓细胞性白血病患者的预后。

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来源期刊

Current Opinion in Hematology 医学-血液学

CiteScore

6.60

自引率

3.10%

发文量

审稿时长

6-12 weeks

期刊介绍： Current Opinion in Hematology is an easy-to-digest bimonthly journal covering the most interesting and important advances in the field of hematology. Its hand-picked selection of editors ensure the highest quality selection of unbiased review articles on themes from nine key subject areas, including myeloid biology, Vascular biology, hematopoiesis and erythroid system and its diseases.