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Ferritin Metabolism Reflects Multiple Myeloma Microenvironment and Predicts Patient Outcome
Multiple myeloma (MM) is a hematologic malignancy with a multistep evolutionary pattern, in which the pro-inflammatory and immunosuppressive microenvironment and genomic instability drive tumor evolution. MM microenvironment is rich in iron, released by pro-inflammatory cells from ferritin macromole...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10218632/ https://www.ncbi.nlm.nih.gov/pubmed/37240197 http://dx.doi.org/10.3390/ijms24108852 |
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author | Plano, Federica Gigliotta, Emilia Corsale, Anna Maria Azgomi, Mojtaba Shekarkar Santonocito, Carlotta Ingrascì, Manuela Di Carlo, Laura Augello, Antonino Elia Speciale, Maria Vullo, Candida Rotolo, Cristina Camarda, Giulia Maria Caccamo, Nadia Meraviglia, Serena Dieli, Francesco Siragusa, Sergio Botta, Cirino |
author_facet | Plano, Federica Gigliotta, Emilia Corsale, Anna Maria Azgomi, Mojtaba Shekarkar Santonocito, Carlotta Ingrascì, Manuela Di Carlo, Laura Augello, Antonino Elia Speciale, Maria Vullo, Candida Rotolo, Cristina Camarda, Giulia Maria Caccamo, Nadia Meraviglia, Serena Dieli, Francesco Siragusa, Sergio Botta, Cirino |
author_sort | Plano, Federica |
collection | PubMed |
description | Multiple myeloma (MM) is a hematologic malignancy with a multistep evolutionary pattern, in which the pro-inflammatory and immunosuppressive microenvironment and genomic instability drive tumor evolution. MM microenvironment is rich in iron, released by pro-inflammatory cells from ferritin macromolecules, which contributes to ROS production and cellular damage. In this study, we showed that ferritin increases from indolent to active gammopathies and that patients with low serum ferritin had longer first line PFS (42.6 vs. 20.7 months and, p = 0.047, respectively) and OS (NR vs. 75.1 months and p = 0.029, respectively). Moreover, ferritin levels correlated with systemic inflammation markers and with the presence of a specific bone marrow cell microenvironment (including increased MM cell infiltration). Finally, we verified by bioinformatic approaches in large transcriptomic and single cell datasets that a gene expression signature associated with ferritin biosynthesis correlated with worse outcome, MM cell proliferation, and specific immune cell profiles. Overall, we provide evidence of the role of ferritin as a predictive/prognostic factor in MM, setting the stage for future translational studies investigating ferritin and iron chelation as new targets for improving MM patient outcome. |
format | Online Article Text |
id | pubmed-10218632 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-102186322023-05-27 Ferritin Metabolism Reflects Multiple Myeloma Microenvironment and Predicts Patient Outcome Plano, Federica Gigliotta, Emilia Corsale, Anna Maria Azgomi, Mojtaba Shekarkar Santonocito, Carlotta Ingrascì, Manuela Di Carlo, Laura Augello, Antonino Elia Speciale, Maria Vullo, Candida Rotolo, Cristina Camarda, Giulia Maria Caccamo, Nadia Meraviglia, Serena Dieli, Francesco Siragusa, Sergio Botta, Cirino Int J Mol Sci Communication Multiple myeloma (MM) is a hematologic malignancy with a multistep evolutionary pattern, in which the pro-inflammatory and immunosuppressive microenvironment and genomic instability drive tumor evolution. MM microenvironment is rich in iron, released by pro-inflammatory cells from ferritin macromolecules, which contributes to ROS production and cellular damage. In this study, we showed that ferritin increases from indolent to active gammopathies and that patients with low serum ferritin had longer first line PFS (42.6 vs. 20.7 months and, p = 0.047, respectively) and OS (NR vs. 75.1 months and p = 0.029, respectively). Moreover, ferritin levels correlated with systemic inflammation markers and with the presence of a specific bone marrow cell microenvironment (including increased MM cell infiltration). Finally, we verified by bioinformatic approaches in large transcriptomic and single cell datasets that a gene expression signature associated with ferritin biosynthesis correlated with worse outcome, MM cell proliferation, and specific immune cell profiles. Overall, we provide evidence of the role of ferritin as a predictive/prognostic factor in MM, setting the stage for future translational studies investigating ferritin and iron chelation as new targets for improving MM patient outcome. MDPI 2023-05-16 /pmc/articles/PMC10218632/ /pubmed/37240197 http://dx.doi.org/10.3390/ijms24108852 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Communication Plano, Federica Gigliotta, Emilia Corsale, Anna Maria Azgomi, Mojtaba Shekarkar Santonocito, Carlotta Ingrascì, Manuela Di Carlo, Laura Augello, Antonino Elia Speciale, Maria Vullo, Candida Rotolo, Cristina Camarda, Giulia Maria Caccamo, Nadia Meraviglia, Serena Dieli, Francesco Siragusa, Sergio Botta, Cirino Ferritin Metabolism Reflects Multiple Myeloma Microenvironment and Predicts Patient Outcome |
title | Ferritin Metabolism Reflects Multiple Myeloma Microenvironment and Predicts Patient Outcome |
title_full | Ferritin Metabolism Reflects Multiple Myeloma Microenvironment and Predicts Patient Outcome |
title_fullStr | Ferritin Metabolism Reflects Multiple Myeloma Microenvironment and Predicts Patient Outcome |
title_full_unstemmed | Ferritin Metabolism Reflects Multiple Myeloma Microenvironment and Predicts Patient Outcome |
title_short | Ferritin Metabolism Reflects Multiple Myeloma Microenvironment and Predicts Patient Outcome |
title_sort | ferritin metabolism reflects multiple myeloma microenvironment and predicts patient outcome |
topic | Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10218632/ https://www.ncbi.nlm.nih.gov/pubmed/37240197 http://dx.doi.org/10.3390/ijms24108852 |
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