Mapping of Functional Metabolic Phenotypes in Acute Myeloid Leukemia

IF 2.9 2区医学 Q2 ONCOLOGY

Cancer Medicine Pub Date : 2025-05-19 DOI:10.1002/cam4.70950

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

{"title":"Mapping of Functional Metabolic Phenotypes in Acute Myeloid Leukemia","authors":"Sissel Dyrstad, Kimberley Joanne Hatfield, Endre Stigen, Marte Karen Brattås, Karl Johan Tronstad, Håkon Reikvam","doi":"10.1002/cam4.70950","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>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 <i>FLT3</i> or <i>NPM1</i>.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>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.</p>\n </section>\n </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 10","pages":""},"PeriodicalIF":2.9000,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70950","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Medicine","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/cam4.70950","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}

引用次数: 0

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.

查看原文本刊更多论文

急性髓系白血病的功能代谢表型定位

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是高度异质性的，受各种染色体、遗传和表观遗传改变的影响。方法研究46例原发性AML细胞的代谢谱，重点研究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耗氧量（OCR）和糖酵解的细胞外酸化率（ECAR）。我们的研究结果显示了代谢活动的显著差异，一些样本更多地依赖于糖酵解而不是线粒体呼吸。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，表明不同的代谢适应。在不良细胞遗传学异常的患者中观察到较高的糖酵解活性。然而，没有发现代谢谱与FLT3或NPM1突变之间的明确关联。这些发现强调了代谢变异性在AML中的作用，并提示针对特定的代谢途径可以提供治疗机会，特别是对于具有独特代谢特征的FAB M4/M5亚群。需要进一步的研究来完善这些治疗策略以用于临床应用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Cancer Medicine ONCOLOGY-

CiteScore

5.50

自引率

2.50%

发文量

907

审稿时长

19 weeks

期刊介绍： Cancer Medicine is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research from global biomedical researchers across the cancer sciences. The journal will consider submissions from all oncologic specialties, including, but not limited to, the following areas: Clinical Cancer Research Translational research ∙ clinical trials ∙ chemotherapy ∙ radiation therapy ∙ surgical therapy ∙ clinical observations ∙ clinical guidelines ∙ genetic consultation ∙ ethical considerations Cancer Biology: Molecular biology ∙ cellular biology ∙ molecular genetics ∙ genomics ∙ immunology ∙ epigenetics ∙ metabolic studies ∙ proteomics ∙ cytopathology ∙ carcinogenesis ∙ drug discovery and delivery. Cancer Prevention: Behavioral science ∙ psychosocial studies ∙ screening ∙ nutrition ∙ epidemiology and prevention ∙ community outreach. Bioinformatics: Gene expressions profiles ∙ gene regulation networks ∙ genome bioinformatics ∙ pathwayanalysis ∙ prognostic biomarkers. Cancer Medicine publishes original research articles, systematic reviews, meta-analyses, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented in the paper.