Effects of IOL in a murine model of MDS. FPN mutation leads to increased GI iron absorption and IOL, in turn leading to inferior erythropoiesis, LFS, and OS. IOL results in formation of ROS, an indicator of oxidative stress. Cellular processes impacted by oxidative stress in preclinical studies are listed in the dashed boxes and lead to HSC death or mutation with MDS progression.2 These effects are reversed by blocking FPN with VIT. Luspatercept plus VIT has an additive beneficial effect on erythropoiesis. ∗, C326S mutation; AML, acute myeloid leukemia; FPN, ferroportin; HSC, hematopoietic stem cell; LFS, leukemia-free survival, MSC, mesenchymal stromal cells; ROS, reactive oxygen species; TF, transcription factor.
