2. Academic Validation
  3. FDA-approved ferumoxytol displays anti-leukaemia efficacy against cells with low ferroportin levels

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

  • Nat Nanotechnol. 2019 Jun;14(6):616-622. doi: 10.1038/s41565-019-0406-1.
Vicenta Trujillo-Alonso 1,  Edwin C Pratt 2 3,  Hongliang Zong 1,  Andres Lara-Martinez 1,  Charalambos Kaittanis 3,  Mohamed O Rabie 1,  Valerie Longo 4,  Michael W Becker 5,  Gail J Roboz 1,  Jan Grimm 6 7 8,  Monica L Guzman 9 10
Affiliations

Affiliations

  • 1 Division of Hematology/Oncology, Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
  • 2 Department of Pharmacology, Weill Cornell Graduate School, New York, NY, USA.
  • 3 Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • 4 Small-Animal Imaging Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • 5 Department of Medicine, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA.
  • 6 Department of Pharmacology, Weill Cornell Graduate School, New York, NY, USA. grimmj@mskcc.org.
  • 7 Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA. grimmj@mskcc.org.
  • 8 Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. grimmj@mskcc.org.
  • 9 Division of Hematology/Oncology, Department of Medicine, Weill Cornell Medical College, New York, NY, USA. mlg2007@med.cornell.edu.
  • 10 Department of Pharmacology, Weill Cornell Graduate School, New York, NY, USA. mlg2007@med.cornell.edu.
PMID: 30911166 DOI: 10.1038/s41565-019-0406-1
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.

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