ArticleHaematologica2013
Iron increases the susceptibility of multiple myeloma cells to bortezomib.
Article in Haematologica, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 54 citations in OpenAlex.
- Bidentate Metal-Binding Motifs in US FDA Approved Small Molecule Drugs.Journal of medicinal chemistry · 2026Review
- Review
- Ferroptosis targeting: a novel therapeutic armamentarium in multiple myeloma.Cancer cell international · 2026Review
- Harnessing ferroptosis for cancer therapy: Mechanisms and therapeutic strategies (Review).Oncology reports · 2026Review
- Targeting STK17B kinase activates ferroptosis and suppresses drug resistance in multiple myeloma.Blood · 2026Article
- Ferroptosis in hematological malignancies: molecular mechanisms and therapeutic potential.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- Peroxiredoxins as novel indicators in multiple myeloma associated with ferroptosis and immune infiltration.Scientific reports · 2025Article
- Prognostic significance of baseline serum ferritin in newly diagnosed multiple myeloma cases: A retrospective study from southern India.The Indian journal of medical research · 2025Article
- Ferroptosis: a novel pharmacological mechanism against multiple myeloma.Frontiers in pharmacology · 2025Review
- Acquired Bortezomib Resistance in Multiple Myeloma: From Mechanisms to Strategy.Current treatment options in oncology · 2024Review
- Unlocking ferroptosis in prostate cancer - the road to novel therapies and imaging markers.Nature reviews. Urology · 2024Review
- Comparison of trace elements in peripheral blood and bone marrow of newly diagnosed multiple myeloma patients.Clinical and experimental medicine · 2024Article
- Targeting ferroptosis for leukemia therapy: exploring novel strategies from its mechanisms and role in leukemia based on nanotechnology.European journal of medical research · 2024Review
- Multiple Myeloma from the Perspective of Pro- and Anti-Oxidative Parameters: Potential for Diagnostic and/or Follow-Up Purposes?Journal of personalized medicine · 2024Article
- SRRM2 may be a potential biomarker and immunotherapy target for multiple myeloma: a real-world study based on flow cytometry detection.Clinical and experimental medicine · 2024Article
- Anaplastic thyroid cancer cells reduce CD71 levels to increase iron overload tolerance.Journal of translational medicine · 2023Article
- The modulation of iron metabolism affects the Rhabdomyosarcoma tumor growth in vitro and in vivo.Clinical and experimental medicine · 2023Article
- The Relationship between Changes in Serum Element Concentrations and Pathological Condition and Disease Status in Japanese Multiple Myeloma Patients: A Pilot Study and Literature Review.Asian Pacific journal of cancer prevention : APJCP · 2023Review
- Ferritin Metabolism Reflects Multiple Myeloma Microenvironment and Predicts Patient Outcome.International journal of molecular sciences · 2023Article
- Comprehensive analysis of ferroptosis-related genes in immune infiltration and prognosis in multiple myeloma.Frontiers in pharmacology · 2023Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Multiple myeloma is a malignant still incurable plasma cell disorder. Pharmacological treatment based on proteasome inhibition has improved patient outcome; however, bortezomib-resistance remains a major clinical problem. Inhibition of proteasome functionality affects cellular iron homeostasis and iron is a potent inducer of reactive oxygen species and cell death, unless safely stored in ferritin. We explored the potential role of iron in bortezomib-resistance. We analyzed iron proteins, oxidative status and cell viability in 7 multiple myeloma cell lines and in plasma cells from 5 patients. Cells were treated with increasing bortezomib concentrations with or without iron supplementation. We reduced ferritin levels by both shRNA technology and by drug-induced iron starvation. Multiple myeloma cell lines are characterized by distinct ferritin levels, which directly correlate with bortezomib resistance. We observed that iron supplementation upon bortezomib promotes protein oxidation and cell death, and that iron toxicity inversely correlates with basal ferritin levels. Bortezomib prevents ferritin upregulation in response to iron, thus limiting the ability to buffer reactive oxygen species. Consequently, reduction of basal ferritin levels increases both bortezomib sensitivity and iron toxicity. In patients' cells, we confirmed that bortezomib prevents ferritin increase, that iron supplementation upon bortezomib increases cell death and that ferritin reduction overcomes bortezomib resistance. Bortezomib affects iron homeostasis, sensitizing cells to oxidative damage. Modulation of iron status is a strategy worth exploring to improve the efficacy of proteasome inhibition therapies.
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