{"title":"OXPHOS mediators in acute myeloid leukemia patients: Prognostic biomarkers and therapeutic targets for personalized medicine.","authors":"Amal Kamal Abdel-Aziz","doi":"10.1186/s12957-024-03581-5","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Despite significant advances in comprehending its tumorigenic role, the prognostic and therapeutic potential of targeting oxidative phosphorylation (OXPHOS) in acute myeloid leukemia (AML) remain obscure.</p><p><strong>Methods: </strong>The prognostic value of ~ 200 mitochondrial/OXPHOS genes as candidate biomarkers was examined in AML patients over ~ 10 years follow-up using Kaplan-Meier and Cox regression analyses. Furthermore, the transcript levels of the assessed markers were inspected in healthy bone marrow tissues and the dependencies of AML cells on the assessed genes were examined.</p><p><strong>Results: </strong>Elevated levels of NADH:ubiquinone oxidoreductase subunit A6 (NDUFA6), succinate dehydrogenase complex flavoprotein subunit A (SDHA), solute carrier family 25 member 12 (SLC25A12), electron transfer flavoprotein subunit beta (ETFB), carnitine palmitoyltransferase 1A (CPT1A) and glutathione peroxidase 4 (GPX4) were associated with poor overall survival of AML patients. SLC25A12, ETFB and CPT1A were overexpressed in AML compared to healthy tissues. Cytochrome B5 type A (CYB5A)<sup>high</sup>, SLC25A12<sup>high</sup> and GPX4<sup>high</sup> AML patients displayed higher levels of circulating and engrafted blasts compared to low-expressing cohorts. NPM1 and SRSF2 mutations were frequent in SDHA<sup>low</sup> and CPT1A<sup>low</sup> AML patients respectively. FLT3-ITD, NPM1 and IDH1 mutations were prevalent in CPT1A<sup>high</sup> AML patients. FLT3-ITD AMLs were more dependent on OXPHOS.</p><p><strong>Conclusions: </strong>This study identifies NDUFA6 and SDHA as novel companion prognostic biomarkers which might present a rational strategy for personalized therapy of AML patients.</p>","PeriodicalId":23856,"journal":{"name":"World Journal of Surgical Oncology","volume":"22 1","pages":"298"},"PeriodicalIF":2.5000,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11559054/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"World Journal of Surgical Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12957-024-03581-5","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Despite significant advances in comprehending its tumorigenic role, the prognostic and therapeutic potential of targeting oxidative phosphorylation (OXPHOS) in acute myeloid leukemia (AML) remain obscure.
Methods: The prognostic value of ~ 200 mitochondrial/OXPHOS genes as candidate biomarkers was examined in AML patients over ~ 10 years follow-up using Kaplan-Meier and Cox regression analyses. Furthermore, the transcript levels of the assessed markers were inspected in healthy bone marrow tissues and the dependencies of AML cells on the assessed genes were examined.
Results: Elevated levels of NADH:ubiquinone oxidoreductase subunit A6 (NDUFA6), succinate dehydrogenase complex flavoprotein subunit A (SDHA), solute carrier family 25 member 12 (SLC25A12), electron transfer flavoprotein subunit beta (ETFB), carnitine palmitoyltransferase 1A (CPT1A) and glutathione peroxidase 4 (GPX4) were associated with poor overall survival of AML patients. SLC25A12, ETFB and CPT1A were overexpressed in AML compared to healthy tissues. Cytochrome B5 type A (CYB5A)high, SLC25A12high and GPX4high AML patients displayed higher levels of circulating and engrafted blasts compared to low-expressing cohorts. NPM1 and SRSF2 mutations were frequent in SDHAlow and CPT1Alow AML patients respectively. FLT3-ITD, NPM1 and IDH1 mutations were prevalent in CPT1Ahigh AML patients. FLT3-ITD AMLs were more dependent on OXPHOS.
Conclusions: This study identifies NDUFA6 and SDHA as novel companion prognostic biomarkers which might present a rational strategy for personalized therapy of AML patients.
期刊介绍:
World Journal of Surgical Oncology publishes articles related to surgical oncology and its allied subjects, such as epidemiology, cancer research, biomarkers, prevention, pathology, radiology, cancer treatment, clinical trials, multimodality treatment and molecular biology. Emphasis is placed on original research articles. The journal also publishes significant clinical case reports, as well as balanced and timely reviews on selected topics.
Oncology is a multidisciplinary super-speciality of which surgical oncology forms an integral component, especially with solid tumors. Surgical oncologists around the world are involved in research extending from detecting the mechanisms underlying the causation of cancer, to its treatment and prevention. The role of a surgical oncologist extends across the whole continuum of care. With continued developments in diagnosis and treatment, the role of a surgical oncologist is ever-changing. Hence, World Journal of Surgical Oncology aims to keep readers abreast with latest developments that will ultimately influence the work of surgical oncologists.