ZIP10 as a potential therapeutic target in acute myeloid leukaemia

Acute myeloid leukaemia (AML) is a haematopoietic malignancy that continues to demonstrate lapses in current treatment modalities as evidenced by therapy refractory disease, disease relapse and high rates of lethality. The influence of nutritional factors, including trace elements, on disease development and progression is not yet well understood. We utilized AML cell lines and patient samples to further investigate zinc homeostasis and the dependency of leukaemic cells on zinc. Compared to control individuals, we found significantly increased zinc levels in malignant blasts with concomitant serum hypozincaemia. Increased cellular zinc levels were accompanied by the upregulation of zinc influx transporters such as ZIP6, ZIP9 and ZIP10. Subsequent in vitro experiments showed the importance of zinc for myeloid cell proliferation, survival and block of differentiation. We validated our results with data from the Leukemia Mile (n = 542) and the BeatAML2.0 study (n = 805). Importantly, we identified ZIP10 (as one of the highly upregulated zinc transporters in malignant blasts) which, when targeted, resulted in impaired zinc uptake and decreased malignant cell growth. These findings suggest that therapeutic approaches that target the zinc influx transporter ZIP10 may offer novel means of treatment for patients suffering from AML.