NOX2 control over energy metabolism plays a role in acute myeloid leukaemia prognosis and survival
Ijurko, Carla (Instituto de Investigación Biomédica de Salamanca)
Romo-González, Marta (Instituto de Investigación Biomédica de Salamanca)
García-Calvo, Clara (Instituto de Investigación Biomédica de Salamanca)
Sardina, José Luis (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Sánchez-Bernal, Carmen (Instituto de Investigación Biomédica de Salamanca)
Sánchez-Yagüe, Jesús (Instituto de Investigación Biomédica de Salamanca)
Elena-Herrmann, Bénédicte (University Grenoble Alpes)
Villaret, Joran (University Grenoble Alpes)
Garrel, Catherine (Department of Biochemistry. Hospital of Grenoble Alpes)
Mondet, Julie (Department of Molecular Pathology. Hospital of Grenoble Alpes)
Mossuz, Pascal (Department of Biological Hematology. Hospital of Grenoble Alpes)
Hernández-Hernández, Ángel (Instituto de Investigación Biomédica de Salamanca)
Universitat Autònoma de Barcelona

Date:	2023
Abstract:	Acute myeloid leukaemia (AML) is a highly heterogeneous disease, however the therapeutic approaches have hardly changed in the last decades. Metabolism rewiring and the enhanced production of reactive oxygen species (ROS) are hallmarks of cancer. A deeper understanding of these features could be instrumental for the development of specific AML-subtypes treatments. NADPH oxidases (NOX), the only cellular system specialised in ROS production, are also involved in leukemic metabolism control. NOX2 shows a variable expression in AML patients, so patients can be classified based on such difference. Here we have analysed whether NOX2 levels are important for AML metabolism control. The lack of NOX2 in AML cells slowdowns basal glycolysis and oxidative phosphorylation (OXPHOS), along with the accumulation of metabolites that feed such routes, and a sharp decrease of glutathione. In addition, we found changes in the expression of 725 genes. Among them, we have discovered a panel of 30 differentially expressed metabolic genes, whose relevance was validated in patients. This panel can segregate AML patients according to CYBB expression, and it can predict patient prognosis and survival. In summary, our data strongly support the relevance of NOX2 for AML metabolism, and highlights the potential of our discoveries in AML prognosis.
Grants:	Agencia Estatal de Investigación PID2020-117692RB-I00 Instituto de Salud Carlos III CP19/00176
Note:	Carla Ijurko and Marta Romo-González were recipient of pre-doctoral fellowships from the Regional Government of Castile and Leon, Spain and ERDF funds. Angel Hernández-Hernández lab is supported by Spanish Government (PID2020-117692RB-I00), Regional Government of Castile & Leon (SA077P20) and Ramón Areces Foundation (CIV17A2822). Jose Luis Sardina lab is supported by Instituto de Salud Carlos III (CP19/00176). NMR analyses were carried out by the GEMELI platform, supported by the program IRICE from the Auvergne-Rhône-Alpes region and MSDAvenir funds (project ERiCAN). We thank Dr. I. García-Tuñón for his help with the CRISPR-CAS9 technique.
Note:	Carla Ijurko and Marta Romo-González were recipient of pre-doctoral fellowships from the Regional Government of Castile and Leon, Spain and ERDF funds. Angel Hernández-Hernández lab is supported by Spanish Government (PID2020-117692RB-I00), Regional Government of Castile & Leon (SA077P20) and Ramón Areces Foundation (CIV17A2822). Jose Luis Sardina lab is supported by Instituto de Salud Carlos III (CP19/00176). NMR analyses were carried out by the GEMELI platform, supported by the program IRICE from the Auvergne-Rhône-Alpes region and MSDAvenir funds (project ERiCAN).
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Acute myeloid leukaemia ; NADPH oxidase ; NOX2 ; CYBB Metabolism
Published in:	Free Radical Biology and Medicine, Vol. 209 (20 2023) , p. 18-28, ISSN 1873-4596

DOI: 10.1016/j.freeradbiomed.2023.10.013

11 p, 6.9 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Josep Carreras Leukaemia Research Institute
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Articles > Published articles