FDA-approved ferumoxytol displays anti-leukaemia efficacy against cells with low ferroportin levels.
Vicenta Trujillo-AlonsoEdwin C PrattHongliang ZongAndres Lara-MartinezCharalambos KaittanisMohamed O RabieValerie LongoMichael W BeckerGail J RobozJan GrimmMonica L GuzmanPublished in: Nature nanotechnology (2019)
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.
Keyphrases
- induced apoptosis
- cell cycle arrest
- iron deficiency
- cell death
- oxidative stress
- clinical trial
- reactive oxygen species
- iron oxide
- liver failure
- poor prognosis
- end stage renal disease
- endoplasmic reticulum stress
- bone marrow
- acute myeloid leukemia
- signaling pathway
- ejection fraction
- peritoneal dialysis
- randomized controlled trial
- binding protein
- prognostic factors
- risk factors
- hepatitis b virus
- replacement therapy