FDA-approved ferumoxytol displays anti-leukaemia efficacy against cells with low ferroportin levels Journal Article
| Authors: | Trujillo-Alonso, V.; Pratt, E. C.; Zong, H.; Lara-Martinez, A.; Kaittanis, C.; Rabie, M. O.; Longo, V.; Becker, M. W.; Roboz, G. J.; Grimm, J.; Guzman, M. L. |
| Article Title: | FDA-approved ferumoxytol displays anti-leukaemia efficacy against cells with low ferroportin levels |
| Abstract: | Acute myeloid leukaemia is a fatal disease for most patients. We have found that ferumoxytol (Feraheme), an FDA-approved iron oxide nanoparticle for iron deficiency treatment, demonstrates an anti-leukaemia effect in vitro and in vivo. Using leukaemia cell lines and primary acute myeloid leukaemia patient samples, we show that low expression of the iron exporter ferroportin results in a susceptibility of these cells via an increase in intracellular iron from ferumoxytol. The reactive oxygen species produced by free ferrous iron lead to increased oxidative stress and cell death. Ferumoxytol treatment results in a significant reduction of disease burden in a murine leukaemia model and patient-derived xenotransplants bearing leukaemia cells with low ferroportin expression. Our findings show how a clinical nanoparticle previously considered largely biologically inert could be rapidly incorporated into clinical trials for patients with leukaemia with low ferroportin levels. © 2019, The Author(s), under exclusive licence to Springer Nature Limited. |
| Keywords: | clinical trial; cell death; cell culture; reactive oxygen species; nanoparticles; patient treatment; iron deficiency; iron oxide nanoparticle; iron oxides; biologically inert; disease burdens; intracellular iron; leukaemia cells |
| Journal Title: | Nature Nanotechnology |
| Volume: | 14 |
| Issue: | 6 |
| ISSN: | 1748-3387 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2019-06-01 |
| Start Page: | 616 |
| End Page: | 622 |
| Language: | English |
| DOI: | 10.1038/s41565-019-0406-1 |
| PUBMED: | 30911166 |
| PROVIDER: | scopus |
| PMCID: | PMC6554053 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 July 2019 -- Source: Scopus |
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