Mitoxantrone ameliorates ineffective erythropoiesis in a β-thalassemia intermedia mouse model

• Evaluating therapeutic effect of mitoxantrone on expanded and ineffective erythropoiesis in β-thalassemia.

• Providing significant pre-clinical evidence for targeting autophagy as a novel therapeutic approach for β-thalassemia.

β-thalassemia is a condition characterized by reduced or absent synthesis of β-globin resulting from genetic mutations, leading to expanded and ineffective erythropoiesis. Mitoxantrone has been widely used clinically as an antitumor agent in light of its ability to inhibit cell proliferation. However, its therapeutic effect on expanded and ineffective erythropoiesis in β-thalassemia is untested. We found that mitoxantrone decreased α-globin precipitates and ameliorated anemia, splenomegaly and ineffective erythropoiesis in the HbbTh3/+ mouse model of β-thalassemia intermedia. The partially reversed ineffective erythropoiesis is a consequence of effects on autophagy as mitochondrial retention and protein levels of mTOR, P62 and LC3 in reticulocytes decreased in mitoxantrone-treated HbbTh3/+ mice. These data provide significant pre-clinical evidence for targeting autophagy as a novel therapeutic approach for β-thalassemia.