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脂质在调控多发性骨髓瘤对铁死亡敏感性中的作用机制

The instrumental role of lipids in governing the sensitivity of multiple myeloma to ferroptosis.

作者信息

Habib Ali, Best Oliver G, Toomes Charlotte E, Wallington-Gates Craig T

机构信息

College of Medicine and Public Health, Flinders University, Bedford Park, SA, 5042, Australia.

School of Health, University of the Sunshine Coast, Sippy Downs, QLD, 4556, Australia.

出版信息

Discov Oncol. 2025 Aug 25;16(1):1612. doi: 10.1007/s12672-025-03444-9.


DOI:10.1007/s12672-025-03444-9
PMID:40853521
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12379672/
Abstract

Multiple myeloma (MM) is a malignancy characterised by the uncontrolled proliferation of clonal plasma cells, primarily within the bone marrow, and is still considered incurable. A significant proportion of patients relapse with drug-refractory disease, necessitating the development of novel therapeutic approaches. Ferroptosis is a recently-characterised form of non-apoptotic programmed cell death, linked to phospholipid peroxidation, that represents a promising approach for the treatment of MM and other cancers, that are refractory to more conventional apoptosis-inducing regimens. A better understanding of the relationship between cellular lipid composition and ferroptosis sensitivity is key to harnessing this form of programmed cell death as a therapeutic approach. In addition to the cellular proportions of phospholipids containing poly- and monounsaturated fatty acids, studies to date indicate that cholesterol levels impact not only the onset and progression of haematological malignancies but also the sensitivity of a variety of different cancers to ferroptosis. Therefore, manipulating the uptake and metabolism of lipids, including glycerophospholipids and cholesterol, may be an effective means of sensitising MM cells to ferroptosis. Findings from the limited number of studies concerning ferroptosis in MM and compelling evidence from other malignancies, provide a strong rationale for further investigation of ferroptosis as a novel therapeutic approach for MM.

摘要

多发性骨髓瘤(MM)是一种恶性肿瘤,其特征是克隆性浆细胞不受控制地增殖,主要发生在骨髓中,目前仍被认为无法治愈。相当一部分患者会复发为难治性疾病,因此需要开发新的治疗方法。铁死亡是一种最近被描述的非凋亡程序性细胞死亡形式,与磷脂过氧化有关,是治疗MM和其他癌症的一种有前景的方法,这些癌症对更传统的诱导凋亡方案具有抗性。更好地理解细胞脂质组成与铁死亡敏感性之间的关系,是将这种程序性细胞死亡形式作为一种治疗方法的关键。除了含有多不饱和脂肪酸和单不饱和脂肪酸的磷脂的细胞比例外,迄今为止的研究表明,胆固醇水平不仅影响血液系统恶性肿瘤的发生和进展,还影响多种不同癌症对铁死亡的敏感性。因此,操纵脂质的摄取和代谢,包括甘油磷脂和胆固醇,可能是使MM细胞对铁死亡敏感的有效手段。关于MM中铁死亡的有限研究结果以及其他恶性肿瘤的有力证据,为进一步研究铁死亡作为MM的一种新治疗方法提供了强有力的理论依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0459/12379672/736203758dc4/12672_2025_3444_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0459/12379672/083d49cd0baf/12672_2025_3444_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0459/12379672/736203758dc4/12672_2025_3444_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0459/12379672/083d49cd0baf/12672_2025_3444_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0459/12379672/736203758dc4/12672_2025_3444_Fig2_HTML.jpg

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本文引用的文献

[1]
Novel (1S,3R)-RSL3-Encapsulated Polyunsaturated Fatty Acid Rich Liposomes Sensitise Multiple Myeloma Cells to Ferroptosis-Mediated Cell Death.

Int J Mol Sci. 2025-7-9

[2]
Simvastatin inhibits PD-L1 via ILF3 to induce ferroptosis in gastric cancer cells.

Cell Death Dis. 2025-3-26

[3]
From Biology to Clinical Practice: The Bone Marrow Microenvironment in Multiple Myeloma.

J Clin Med. 2025-1-8

[4]
Bone marrow stromal cells protect myeloma cells from ferroptosis through GPX4 deSUMOylation.

Cancer Lett. 2024-12-7

[5]
ACSL4-mediated lipid rafts prevent membrane rupture and inhibit immunogenic cell death in melanoma.

Cell Death Dis. 2024-9-29

[6]
Cholesterol Depletion-Enhanced Ferroptosis and Immunotherapy via Engineered Nanozyme.

Adv Sci (Weinh). 2024-10

[7]
Class II ferroptosis inducers are a novel therapeutic approach for t(4;14)-positive multiple myeloma.

Blood Adv. 2024-10-8

[8]
Leukocyte immunoglobulin-like receptor B1 (LILRB1) protects human multiple myeloma cells from ferroptosis by maintaining cholesterol homeostasis.

Nat Commun. 2024-7-9

[9]
Cholesterol metabolism in tumor microenvironment: cancer hallmarks and therapeutic opportunities.

Int J Biol Sci. 2024-3-17

[10]
Bone marrow stromal cells dictate lanosterol biosynthesis and ferroptosis of multiple myeloma.

Oncogene. 2024-5

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