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...

Full description

Saved in:

Bibliographic Details
Published in:	International journal of molecular sciences Vol. 24; no. 10; p. 8852
Main Authors:	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
Format:	Journal Article
Language:	English
Published:	Switzerland MDPI AG 16-05-2023 MDPI
Subjects:	Biosynthesis Bone marrow Bone Marrow - metabolism bone marrow microenvironment Cell proliferation Cellular manufacture Chelation Communication Creatinine Ferritin Ferritins - genetics Ferritins - metabolism Gammopathy Gene expression Gene Expression Profiling Genes Genomic instability Hemoglobin Humans Immune system Inflammation Laboratories Macromolecules Malignancy Medical research Medicine, Experimental Metastases Microenvironments monoclonal gammopathy of undetermined significance Monoclonal Gammopathy of Undetermined Significance - pathology Multiple myeloma Multiple Myeloma - pathology Oxidative stress Patient outcomes Patients Physiological aspects Plasma smoldering myeloma Transcriptomics Tumor Microenvironment - genetics smoldering myeloma ferritin multiple myeloma monoclonal gammopathy of undetermined significance bone marrow microenvironment
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	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, = 0.047, respectively) and OS (NR vs. 75.1 months and = 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1422-0067 1661-6596 1422-0067
DOI:	10.3390/ijms24108852