Abstract: The invention relates to methods of treating functional iron deficiency (FID) associated with low, very low, or intermediate risk myelodysplastic syndromes. FID associated with primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (post-PV MF), or post-essential thrombocythemia myelofibrosis (post-ET MF), and FID associated with myelodysplastic syndromes/myeloproliferative neoplasm (MPN) overlap syndromes using small molecule ALK2 inhibitors.

Abstract: The invention features methods of treating a subject receiving a cytopenia-associated myelofibrosis treatment by co-administering an activin receptor type II (ActRII) signaling inhibitor. The ActRII signaling inhibitor may be an antibody that binds to an ActRII ligand, an ActRII antibody, or an ActRII ligand trap.

Abstract: The invention features polypeptides that include an extracellular ActRII chimera. In some embodiments, a polypeptide of the invention includes an extracellular ActRII chimera fused to an Fc domain or moiety. The invention also features pharmaceutical compositions and methods of using the polypeptides to treat diseases and conditions involving weakness or atrophy of muscles, bone damage, low red blood cell levels (e.g., anemia or blood loss), low platelet levels (e.g., thrombocytopenia), low neutrophil levels (e.g., neutropenia), fibrosis, metabolic disorders, pulmonary hypertension, and/or diseases and conditions that can be treated with erythropoietin or an erythropoiesis-stimulating agent.

Abstract: The invention features methods of treating a subject having a cytopenia associated with a myelodysplastic syndrome, a cytopenia associated with chronic myelomonocytic leukemia, or a cytopenia associated with myelofibrosis, such as anemia, thrombocytopenia, or neutropenia, by administering to the subject an ActRII signaling inhibitor, such as an ActRIIA ligand trap including an extracellular ActRIIA variant. The extracellular ActRIIA variant may be fused to an Fc domain or moiety.

Abstract: The invention features methods of treating iron overload in a subject by administering BMP or hepcidin inhibitors, such as ALK2 inhibitors. The invention also features methods of decreasing iron levels in a subject by administering BMP or hepcidin inhibitors.

Abstract: The invention features methods of treating or preventing the development of a cardiovascular-related disease by administering to the subject a BMP inhibitor or a hepcidin inhibitor, such as an ALK2 inhibitor.

Abstract: The invention features methods of treating or preventing lymphopenia in a subject treated with a BMP inhibitor or a hepcidin inhibitor, such as an ALK2 inhibitor, by co-administering an iron supplement with the inhibitor, and methods of treating a subject who has or is at risk of developing a disease or condition that can be treated with a BMP inhibitor or a hepcidin inhibitor, such as an ALK2 inhibitor, by administering to the subject a BMP inhibitor or a hepcidin inhibitor and an iron supplement.

Abstract: The invention features polypeptides that include an extracellular ActRII variant, such as an ActRIIA variant, ActRIIB variant, or ActRII chimera. In some embodiments, a polypeptide of the invention includes an extracellular ActRII variant fused to an Fc domain monomer or moiety. The invention also features pharmaceutical compositions containing said polypeptides and methods of using the polypeptides to treat diseases and conditions that can be treated with erythropoietin or an erythropoiesis-stimulating agent.