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


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.

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The data that support the plots within this paper and other findings of this study are available from the corresponding author upon reasonable request.

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Journal peer review information: Nature Nanotechnology thanks Kamil Kranc and other anonymous reviewer(s) for their contribution to the peer review of this work.

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This work was supported by the following grants: National Institutes of Health (NIH) R01CA218615 and R01CA215700 (to J.G.), P30 CA08748 (to C. Thompson, MSKCC) and R01CA172546 and R01CA102031 (to M.L.G.), an ALSF for Childhood Cancer Research award (to C.K.), Mr William H. and Mrs Alice Goodwin and the Commonwealth Foundation for Cancer Research and The Center for Experimental Therapeutics of Memorial Sloan Kettering Cancer Center (to J.G. as co-PI). J.G.’s primary affiliation is the Molecular Pharmacology program of Memorial Sloan Kettering Cancer Center with a secondary appointment at its Radiology Department. He also has an appointment at the Pharmacology Program at Weil Cornell Medical College. Affiliations are listed in order of the authors.

Author information

V.T.-A., E.C.P., H.Z., C.K., J.G. and M.L.G. devised and conducted experiments and wrote the manuscript. A.L.-M. and M.O.R. performed experiments. M.W.B. and G.J.R. discussed the data and wrote the manuscript. V.L. conducted injections.

Competing interests

J.G., C.K., H.Z. and M.L.G. have filed pending US patent application 15/759,161 and pending EU application 16,845,094.8 around the therapeutic use of ferumoxytol. C.K. is currently an employee of Alnylam Pharmaceuticals.

Correspondence to Jan Grimm or Monica L. Guzman.

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Supplementary Tables 1–4, Supplementary Figures 1–17

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Further reading

Fig. 1: Reduced expression of FPN is a feature of leukaemia cell lines and primary AML samples.
Fig. 2: In vivo treatment of mice having blast crisis CML with ferumoxytol reduces leukaemia burden and improves overall survival.
Fig. 3: Ferumoxytol treatment targets primary AML PDXs with low FPN without harming normal cells.
Fig. 4: Oxidative ferrotherapy through low FPN expression in leukaemia cells.