Division of Hematology/Oncology, Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
Department of Pharmacology, Weill Cornell Graduate School, New York, NY, USA.
Nat Nanotechnol. 2019 Jun;14(6):616-622. doi: 10.1038/s41565-019-0406-1. Epub 2019 Mar 25.
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.
急性髓系白血病（AML）对大多数患者来说是一种致命疾病。我们发现，FDA 批准的用于治疗缺铁症的氧化铁纳米颗粒 ferumoxytol（Feraheme）在体外和体内均具有抗白血病作用。通过使用白血病细胞系和原发性急性髓系白血病患者样本，我们表明，铁输出蛋白 ferroportin 的低表达会导致这些细胞因 ferumoxytol 增加细胞内铁而变得易感性。游离二价铁产生的活性氧会导致氧化应激增加和细胞死亡。Ferumoxytol 治疗可显著降低白血病小鼠模型和携带低 ferroportin 表达白血病细胞的患者来源异种移植模型中的疾病负担。我们的研究结果表明，一种先前被认为在生物学上基本惰性的临床纳米颗粒，如何能够迅速被纳入低 ferroportin 水平白血病患者的临床试验中。
