Selenium Supplementation As a Cure for Leukemia – Eradication of Leukemic Stem Cells

The micronutrient selenium (Se) has been demonstrated to have anti‐leukemic effects but there are no studies showing the ability of Se to affect leukemia stem cells (LSC), which are responsible for maintenance and relapse. We hypothesize that Se can specifically target LSCs via their ability to shunt arachidonic acid metabolism towards cyclooxygenase (COX)‐derived pro‐apoptotic metabolite, 15d‐prostaglandin (PG) J2 in vivo. We have used three murine models of leukemia involving transplantation of BCR‐ABL‐transduced LSCs, MLL‐AF9‐transduced LSCs, or infection with Friend virus. In all these models, mice on Se‐deficient (0.01 ppm selenite) or Se‐adequate (0.1 ppm selenite) diets succumbed to leukemia; while the mice maintained on Se‐supplemented (0.4 ppm selenite) diets displayed absence of disease with normal WBC counts and spleen size, and an absence of LSCs (Kit+Sca+). These effects of Se were blocked when the mice were treated with a COX‐inhibitor, indomethacin, suggesting that COX metabolites play a pivotal role. Furthermore, upon comparing the effect of conventionally used chemotherapeutic agent imatinib with that of Se supplementation, mice in the former group showed relapse of disease upon discontinuation of therapy. All these studies show that Se taken in supplemental quantities can potentially cure leukemia by selectively eradicating LSCs via anti‐proliferative COX metabolites. NIH DK077152Grant Funding Source : NIH DK077152