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.

Plano, F., Gigliotta, E., Corsale, A.M., Azgomi, M.S., Santonocito, C., Ingrascì, M., et al. (2023). Ferritin Metabolism Reflects Multiple Myeloma Microenvironment and Predicts Patient Outcome. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 24(10) [10.3390/ijms24108852].

Ferritin Metabolism Reflects Multiple Myeloma Microenvironment and Predicts Patient Outcome

Plano, Federica
Primo
;
Gigliotta, Emilia;Corsale, Anna Maria;Azgomi, Mojtaba Shekarkar;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
Ultimo
2023-01-01

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.
2023
Plano, F., Gigliotta, E., Corsale, A.M., Azgomi, M.S., Santonocito, C., Ingrascì, M., et al. (2023). Ferritin Metabolism Reflects Multiple Myeloma Microenvironment and Predicts Patient Outcome. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 24(10) [10.3390/ijms24108852].
File in questo prodotto:
File Dimensione Formato  
ijms-24-08852.pdf

accesso aperto

Tipologia: Versione Editoriale
Dimensione 4.15 MB
Formato Adobe PDF
4.15 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10447/589996
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 2
  • ???jsp.display-item.citation.isi??? 2
social impact