Figure 3. Schematic depiction of SMAD2/3 ligand trapping by luspatercept to treat impaired erythroid maturation and alleviate ineffective erythropoiesis.

(A) Ineffective erythropoiesis is the inability to produce an adequate number of red blood cells despite the presence of increased numbers of immature erythroid precursors driven by elevated EPO in response to general hypoxia. Elevated levels of SMAD2/3 signaling contribute to impaired erythroid maturation. (B) Sequestration of SMAD2/3-pathway ligands by therapeutic treatment with activin receptor–based traps such as luspatercept can restore erythroid maturation and alleviate anemia.