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A 29‐gene signature associated with NOX2 discriminates acute myeloid leukemia prognosis and survival

The molecular complexity displayed in acute myeloid leukemia (AML) hinders patient stratification and treatment decisions. Previous studies support the utility of using specific gene panels for this purpose. Focusing on two salient features of AML, the production of reactive oxygen species (ROS) by...

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Autores principales: Ijurko, Carla, González‐García, Nerea, Galindo‐Villardón, Purificación, Hernández‐Hernández, Ángel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9303675/
https://www.ncbi.nlm.nih.gov/pubmed/35073432
http://dx.doi.org/10.1002/ajh.26477
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author Ijurko, Carla
González‐García, Nerea
Galindo‐Villardón, Purificación
Hernández‐Hernández, Ángel
author_facet Ijurko, Carla
González‐García, Nerea
Galindo‐Villardón, Purificación
Hernández‐Hernández, Ángel
author_sort Ijurko, Carla
collection PubMed
description The molecular complexity displayed in acute myeloid leukemia (AML) hinders patient stratification and treatment decisions. Previous studies support the utility of using specific gene panels for this purpose. Focusing on two salient features of AML, the production of reactive oxygen species (ROS) by NADPH oxidases (NOX) and metabolism, we aimed to identify a gene panel that could improve patient stratification. A pairwise comparison of AML versus healthy gene expression revealed the downregulation of four members of the NOX2 complex including CYBB (coding for NOX2) in AML patients. We analyzed the expression of 941 genes related to metabolism and found 28 genes with expression correlated to CYBB. This panel of 29 genes (29G) effectively divides AML samples according to their prognostic group. The robustness of 29G was confirmed by 6 AML cohort datasets with a total of 1821 patients (overall accuracies of 85%, 78%, 80%, 75%, 59% and 83%). An expression index (EI) was developed according to the expression of the selected discriminatory genes. Overall Survival (OS) was higher for low 29G expression index patients than for the high 29G expression index group, which was confirmed in three different datasets with a total of 1069 patients. Moreover, 29G can dissect intermediate‐prognosis patients in four clusters with different OS, which could improve the current AML stratification scheme. In summary, we have found a gene signature (29G) that can be used for AML classification and for OS prediction. Our results confirm NOX and metabolism as suitable therapeutic targets in AML.
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spelling pubmed-93036752022-07-28 A 29‐gene signature associated with NOX2 discriminates acute myeloid leukemia prognosis and survival Ijurko, Carla González‐García, Nerea Galindo‐Villardón, Purificación Hernández‐Hernández, Ángel Am J Hematol Research Articles The molecular complexity displayed in acute myeloid leukemia (AML) hinders patient stratification and treatment decisions. Previous studies support the utility of using specific gene panels for this purpose. Focusing on two salient features of AML, the production of reactive oxygen species (ROS) by NADPH oxidases (NOX) and metabolism, we aimed to identify a gene panel that could improve patient stratification. A pairwise comparison of AML versus healthy gene expression revealed the downregulation of four members of the NOX2 complex including CYBB (coding for NOX2) in AML patients. We analyzed the expression of 941 genes related to metabolism and found 28 genes with expression correlated to CYBB. This panel of 29 genes (29G) effectively divides AML samples according to their prognostic group. The robustness of 29G was confirmed by 6 AML cohort datasets with a total of 1821 patients (overall accuracies of 85%, 78%, 80%, 75%, 59% and 83%). An expression index (EI) was developed according to the expression of the selected discriminatory genes. Overall Survival (OS) was higher for low 29G expression index patients than for the high 29G expression index group, which was confirmed in three different datasets with a total of 1069 patients. Moreover, 29G can dissect intermediate‐prognosis patients in four clusters with different OS, which could improve the current AML stratification scheme. In summary, we have found a gene signature (29G) that can be used for AML classification and for OS prediction. Our results confirm NOX and metabolism as suitable therapeutic targets in AML. John Wiley & Sons, Inc. 2022-02-08 2022-04 /pmc/articles/PMC9303675/ /pubmed/35073432 http://dx.doi.org/10.1002/ajh.26477 Text en © 2022 The Authors. American Journal of Hematology published by Wiley Periodicals LLC. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Research Articles
Ijurko, Carla
González‐García, Nerea
Galindo‐Villardón, Purificación
Hernández‐Hernández, Ángel
A 29‐gene signature associated with NOX2 discriminates acute myeloid leukemia prognosis and survival
title A 29‐gene signature associated with NOX2 discriminates acute myeloid leukemia prognosis and survival
title_full A 29‐gene signature associated with NOX2 discriminates acute myeloid leukemia prognosis and survival
title_fullStr A 29‐gene signature associated with NOX2 discriminates acute myeloid leukemia prognosis and survival
title_full_unstemmed A 29‐gene signature associated with NOX2 discriminates acute myeloid leukemia prognosis and survival
title_short A 29‐gene signature associated with NOX2 discriminates acute myeloid leukemia prognosis and survival
title_sort 29‐gene signature associated with nox2 discriminates acute myeloid leukemia prognosis and survival
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9303675/
https://www.ncbi.nlm.nih.gov/pubmed/35073432
http://dx.doi.org/10.1002/ajh.26477
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