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Iron overload alters the energy metabolism in patients with myelodysplastic syndromes: results from the multicenter FISM BIOFER study

Myelodysplastic syndromes (MDS) are hematological malignancies characterized by ineffective hematopoiesis and increased apoptosis in the bone marrow, which cause peripheral cytopenia. Mitochondria are key regulators of apoptosis and a site of iron accumulation that favors reactive oxygen species (RO...

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Autores principales: Cilloni, Daniela, Ravera, Silvia, Calabrese, Chiara, Gaidano, Valentina, Niscola, Pasquale, Balleari, Enrico, Gallo, Daniela, Petiti, Jessica, Signorino, Elisabetta, Rosso, Valentina, Panuzzo, Cristina, Sabatini, Federica, Andreani, Giacomo, Dragani, Matteo, Finelli, Carlo, Poloni, Antonella, Crugnola, Monica, Voso, Maria Teresa, Fenu, Susanna, Pelizzari, Annamaria, Santini, Valeria, Saglio, Giuseppe, Podestà, Marina, Frassoni, Francesco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280296/
https://www.ncbi.nlm.nih.gov/pubmed/32514107
http://dx.doi.org/10.1038/s41598-020-66162-y
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author Cilloni, Daniela
Ravera, Silvia
Calabrese, Chiara
Gaidano, Valentina
Niscola, Pasquale
Balleari, Enrico
Gallo, Daniela
Petiti, Jessica
Signorino, Elisabetta
Rosso, Valentina
Panuzzo, Cristina
Sabatini, Federica
Andreani, Giacomo
Dragani, Matteo
Finelli, Carlo
Poloni, Antonella
Crugnola, Monica
Voso, Maria Teresa
Fenu, Susanna
Pelizzari, Annamaria
Santini, Valeria
Saglio, Giuseppe
Podestà, Marina
Frassoni, Francesco
author_facet Cilloni, Daniela
Ravera, Silvia
Calabrese, Chiara
Gaidano, Valentina
Niscola, Pasquale
Balleari, Enrico
Gallo, Daniela
Petiti, Jessica
Signorino, Elisabetta
Rosso, Valentina
Panuzzo, Cristina
Sabatini, Federica
Andreani, Giacomo
Dragani, Matteo
Finelli, Carlo
Poloni, Antonella
Crugnola, Monica
Voso, Maria Teresa
Fenu, Susanna
Pelizzari, Annamaria
Santini, Valeria
Saglio, Giuseppe
Podestà, Marina
Frassoni, Francesco
author_sort Cilloni, Daniela
collection PubMed
description Myelodysplastic syndromes (MDS) are hematological malignancies characterized by ineffective hematopoiesis and increased apoptosis in the bone marrow, which cause peripheral cytopenia. Mitochondria are key regulators of apoptosis and a site of iron accumulation that favors reactive oxygen species (ROS) production with detrimental effects on cell survival. Although the energy metabolism could represent an attractive therapeutic target, it was poorly investigated in MDS. The purpose of the study was to analyze how the presence of myelodysplastic hematopoiesis, iron overload and chelation impact on mitochondrial metabolism. We compared energy balance, OxPhos activity and efficiency, lactic dehydrogenase activity and lipid peroxidation in mononuclear cells (MNCs), isolated from 38 MDS patients and 79 healthy controls. Our data show that ATP/AMP ratio is reduced during aging and even more in MDS due to a decreased OxPhos activity associated with an increment of lipid peroxidation. Moreover, the lactate fermentation enhancement was observed in MDS and elderly subjects, probably as an attempt to restore the energy balance. The biochemical alterations of MNCs from MDS patients have been partially restored by the in vitro iron chelation, while only slight effects were observed in the age-matched control samples. By contrast, the addition of iron chelators on MNCs from young healthy subjects determined a decrement in the OxPhos efficiency and an increment of lactate fermentation and lipid peroxidation. In summary, MDS-MNCs display an altered energy metabolism associated with increased oxidative stress, due to iron accumulation. This condition could be partially restored by iron chelation.
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spelling pubmed-72802962020-06-15 Iron overload alters the energy metabolism in patients with myelodysplastic syndromes: results from the multicenter FISM BIOFER study Cilloni, Daniela Ravera, Silvia Calabrese, Chiara Gaidano, Valentina Niscola, Pasquale Balleari, Enrico Gallo, Daniela Petiti, Jessica Signorino, Elisabetta Rosso, Valentina Panuzzo, Cristina Sabatini, Federica Andreani, Giacomo Dragani, Matteo Finelli, Carlo Poloni, Antonella Crugnola, Monica Voso, Maria Teresa Fenu, Susanna Pelizzari, Annamaria Santini, Valeria Saglio, Giuseppe Podestà, Marina Frassoni, Francesco Sci Rep Article Myelodysplastic syndromes (MDS) are hematological malignancies characterized by ineffective hematopoiesis and increased apoptosis in the bone marrow, which cause peripheral cytopenia. Mitochondria are key regulators of apoptosis and a site of iron accumulation that favors reactive oxygen species (ROS) production with detrimental effects on cell survival. Although the energy metabolism could represent an attractive therapeutic target, it was poorly investigated in MDS. The purpose of the study was to analyze how the presence of myelodysplastic hematopoiesis, iron overload and chelation impact on mitochondrial metabolism. We compared energy balance, OxPhos activity and efficiency, lactic dehydrogenase activity and lipid peroxidation in mononuclear cells (MNCs), isolated from 38 MDS patients and 79 healthy controls. Our data show that ATP/AMP ratio is reduced during aging and even more in MDS due to a decreased OxPhos activity associated with an increment of lipid peroxidation. Moreover, the lactate fermentation enhancement was observed in MDS and elderly subjects, probably as an attempt to restore the energy balance. The biochemical alterations of MNCs from MDS patients have been partially restored by the in vitro iron chelation, while only slight effects were observed in the age-matched control samples. By contrast, the addition of iron chelators on MNCs from young healthy subjects determined a decrement in the OxPhos efficiency and an increment of lactate fermentation and lipid peroxidation. In summary, MDS-MNCs display an altered energy metabolism associated with increased oxidative stress, due to iron accumulation. This condition could be partially restored by iron chelation. Nature Publishing Group UK 2020-06-08 /pmc/articles/PMC7280296/ /pubmed/32514107 http://dx.doi.org/10.1038/s41598-020-66162-y Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Cilloni, Daniela
Ravera, Silvia
Calabrese, Chiara
Gaidano, Valentina
Niscola, Pasquale
Balleari, Enrico
Gallo, Daniela
Petiti, Jessica
Signorino, Elisabetta
Rosso, Valentina
Panuzzo, Cristina
Sabatini, Federica
Andreani, Giacomo
Dragani, Matteo
Finelli, Carlo
Poloni, Antonella
Crugnola, Monica
Voso, Maria Teresa
Fenu, Susanna
Pelizzari, Annamaria
Santini, Valeria
Saglio, Giuseppe
Podestà, Marina
Frassoni, Francesco
Iron overload alters the energy metabolism in patients with myelodysplastic syndromes: results from the multicenter FISM BIOFER study
title Iron overload alters the energy metabolism in patients with myelodysplastic syndromes: results from the multicenter FISM BIOFER study
title_full Iron overload alters the energy metabolism in patients with myelodysplastic syndromes: results from the multicenter FISM BIOFER study
title_fullStr Iron overload alters the energy metabolism in patients with myelodysplastic syndromes: results from the multicenter FISM BIOFER study
title_full_unstemmed Iron overload alters the energy metabolism in patients with myelodysplastic syndromes: results from the multicenter FISM BIOFER study
title_short Iron overload alters the energy metabolism in patients with myelodysplastic syndromes: results from the multicenter FISM BIOFER study
title_sort iron overload alters the energy metabolism in patients with myelodysplastic syndromes: results from the multicenter fism biofer study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280296/
https://www.ncbi.nlm.nih.gov/pubmed/32514107
http://dx.doi.org/10.1038/s41598-020-66162-y
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