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Communication

Ferritin Metabolism Reflects Multiple Myeloma Microenvironment and Predicts Patient Outcome

by
Federica Plano
1,
Emilia Gigliotta
1,
Anna Maria Corsale
1,
Mojtaba Shekarkar Azgomi
1,
Carlotta Santonocito
1,
Manuela Ingrascì
1,
Laura Di Carlo
1,
Antonino Elia Augello
1,
Maria Speciale
1,
Candida Vullo
1,
Cristina Rotolo
1,
Giulia Maria Camarda
1,
Nadia Caccamo
2,
Serena Meraviglia
2,
Francesco Dieli
2,
Sergio Siragusa
1 and
Cirino Botta
1,*
1
Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, 90127 Palermo, Italy
2
Department of Biomedicine, Neurosciences and Advanced Diagnosis, University of Palermo, 90127 Palermo, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2023, 24(10), 8852; https://doi.org/10.3390/ijms24108852
Submission received: 6 February 2023 / Revised: 28 April 2023 / Accepted: 3 May 2023 / Published: 16 May 2023
(This article belongs to the Special Issue Recent Advance on Iron Metabolism, Ferritin and Hepcidin Research)
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Abstract

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.
Keywords: multiple myeloma; smoldering myeloma; monoclonal gammopathy of undetermined significance; ferritin; bone marrow microenvironment multiple myeloma; smoldering myeloma; monoclonal gammopathy of undetermined significance; ferritin; bone marrow microenvironment

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MDPI and ACS Style

Plano, F.; Gigliotta, E.; Corsale, A.M.; Azgomi, M.S.; Santonocito, C.; Ingrascì, M.; Di Carlo, L.; Augello, A.E.; Speciale, M.; Vullo, C.; et al. Ferritin Metabolism Reflects Multiple Myeloma Microenvironment and Predicts Patient Outcome. Int. J. Mol. Sci. 2023, 24, 8852. https://doi.org/10.3390/ijms24108852

AMA Style

Plano F, Gigliotta E, Corsale AM, Azgomi MS, Santonocito C, Ingrascì M, Di Carlo L, Augello AE, Speciale M, Vullo C, et al. Ferritin Metabolism Reflects Multiple Myeloma Microenvironment and Predicts Patient Outcome. International Journal of Molecular Sciences. 2023; 24(10):8852. https://doi.org/10.3390/ijms24108852

Chicago/Turabian Style

Plano, Federica, Emilia Gigliotta, Anna Maria Corsale, Mojtaba Shekarkar Azgomi, Carlotta Santonocito, Manuela Ingrascì, Laura Di Carlo, Antonino Elia Augello, Maria Speciale, Candida Vullo, and et al. 2023. "Ferritin Metabolism Reflects Multiple Myeloma Microenvironment and Predicts Patient Outcome" International Journal of Molecular Sciences 24, no. 10: 8852. https://doi.org/10.3390/ijms24108852

APA Style

Plano, F., Gigliotta, E., Corsale, A. M., Azgomi, M. S., Santonocito, C., Ingrascì, M., Di Carlo, L., Augello, A. E., Speciale, M., Vullo, C., Rotolo, C., Camarda, G. M., Caccamo, N., Meraviglia, S., Dieli, F., Siragusa, S., & Botta, C. (2023). Ferritin Metabolism Reflects Multiple Myeloma Microenvironment and Predicts Patient Outcome. International Journal of Molecular Sciences, 24(10), 8852. https://doi.org/10.3390/ijms24108852

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