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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.

SUBMITTER: Trujillo-Alonso V

PROVIDER: S-EPMC6554053 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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FDA-approved ferumoxytol displays anti-leukaemia efficacy against cells with low ferroportin levels.

Trujillo-Alonso Vicenta V Pratt Edwin C EC Zong Hongliang H Lara-Martinez Andres A Kaittanis Charalambos C Rabie Mohamed O MO Longo Valerie V Becker Michael W MW Roboz Gail J GJ Grimm Jan J Guzman Monica L ML

Nature nanotechnology 20190325 6

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 spec ...[more]

PMID: 30911166

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Dataset Information

FDA-approved ferumoxytol displays anti-leukaemia efficacy against cells with low ferroportin levels.

Publications

FDA-approved ferumoxytol displays anti-leukaemia efficacy against cells with low ferroportin levels.

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