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急性髓系白血病中功能代谢表型的图谱绘制

Mapping of Functional Metabolic Phenotypes in Acute Myeloid Leukemia.

作者信息

Dyrstad Sissel, Hatfield Kimberley Joanne, Stigen Endre, Brattås Marte Karen, Tronstad Karl Johan, Reikvam Håkon

机构信息

Department of Biomedicine, Faculty of Medicine, University of Bergen, Bergen, Norway.

Department of Immunology and Transfusion Medicine, Haukeland University Hospital, Bergen, Norway.

出版信息

Cancer Med. 2025 May;14(10):e70950. doi: 10.1002/cam4.70950.

DOI:10.1002/cam4.70950
PMID:40386930
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12086641/
Abstract

BACKGROUND

Acute myeloid leukemia (AML) is an aggressive hematologic malignancy with a poor prognosis, particularly in older patients. AML is highly heterogeneous, influenced by various chromosomal, genetic, and epigenetic alterations.

METHODS

This study investigated the metabolic profiles of primary AML cells from 46 patients, focusing on mitochondrial respiration and glycolysis. We hypothesized that the metabolic profiles would reflect distinct disease characteristics. Using Seahorse technology, we measured the oxygen consumption rate (OCR) for mitochondrial respiration and the extracellular acidification rate (ECAR) for glycolysis.

RESULTS

Our results showed significant variability in metabolic activity, with some samples relying more on glycolysis than mitochondrial respiration. Mature AML cells (FAB M4/M5, CD34 negative) exhibited increased rates of both mitochondrial respiration and glycolysis, indicating distinct metabolic adaptations. Higher glycolytic activity was observed in patients with adverse cytogenetic abnormalities. However, no clear associations were found between metabolic profiles and mutations in FLT3 or NPM1.

CONCLUSION

These findings highlight the role of metabolic variability in AML and suggest that targeting specific metabolic pathways could offer therapeutic opportunities, particularly for subgroups like FAB M4/M5 with unique metabolic features. Further studies are needed to refine these therapeutic strategies for clinical application.

摘要

背景

急性髓系白血病（AML）是一种侵袭性血液系统恶性肿瘤，预后较差，尤其是在老年患者中。AML具有高度异质性，受多种染色体、基因和表观遗传改变的影响。

方法

本研究调查了46例患者原发性AML细胞的代谢谱，重点关注线粒体呼吸和糖酵解。我们假设代谢谱将反映不同的疾病特征。使用海马技术，我们测量了线粒体呼吸的氧消耗率（OCR）和糖酵解的细胞外酸化率（ECAR）。

结果

我们的结果显示代谢活性存在显著差异，一些样本更多地依赖糖酵解而非线粒体呼吸。成熟AML细胞（FAB M4/M5，CD34阴性）表现出线粒体呼吸和糖酵解速率增加，表明有独特的代谢适应性。在具有不良细胞遗传学异常的患者中观察到更高的糖酵解活性。然而，在代谢谱与FLT3或NPM1突变之间未发现明确关联。

结论

这些发现突出了代谢变异性在AML中的作用，并表明靶向特定代谢途径可能提供治疗机会，特别是对于具有独特代谢特征的FAB M4/M5等亚组。需要进一步研究以完善这些治疗策略用于临床应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e78c/12086641/37b37493de87/CAM4-14-e70950-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e78c/12086641/a1c2c9a2232a/CAM4-14-e70950-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e78c/12086641/3d379ae713b2/CAM4-14-e70950-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e78c/12086641/0f617b67207e/CAM4-14-e70950-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e78c/12086641/165a4a41e58e/CAM4-14-e70950-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e78c/12086641/87a48e9f32e2/CAM4-14-e70950-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e78c/12086641/9196a639c231/CAM4-14-e70950-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e78c/12086641/37b37493de87/CAM4-14-e70950-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e78c/12086641/a1c2c9a2232a/CAM4-14-e70950-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e78c/12086641/3d379ae713b2/CAM4-14-e70950-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e78c/12086641/0f617b67207e/CAM4-14-e70950-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e78c/12086641/165a4a41e58e/CAM4-14-e70950-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e78c/12086641/87a48e9f32e2/CAM4-14-e70950-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e78c/12086641/9196a639c231/CAM4-14-e70950-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e78c/12086641/37b37493de87/CAM4-14-e70950-g003.jpg

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