![Systemic iron homeostasis and its regulation by the hepcidin-ferroportin axis. Momelotinib suppresses hepcidin expression in the liver via inhibition of the bone morphogenetic protein (BMP) 6/activin A receptor type 1 (ACVR1)/small mothers against decapentaplegic (SMAD) and interleukin 6 (IL-6)/JAK/STAT3 pathways, leading to reduced sequestration of iron in the reticuloendothelial system and enhanced iron availability for bone marrow erythropoiesis. Hepcidin is elevated in patients with MF due to aberrant hyperactivation of signaling via the BMP6-stimulated kinase, ACVR1/ALK2, and inflammatory cytokine signaling via IL-6, which is also elevated in patients with MF. Suppression of hepcidin expression in the liver increases circulating iron (transferrin [Tf]-Fe3+]2) and hemoglobin and stimulates erythropoiesis in the bone marrow. The lower panel lists the major causes of anemia in myelofibrosis. EPO, erythropoietin; ERFE, erythroferrone; H, hepcidin; MMB, momelotinib; RBC, red blood cell. Modified, with permission, from Chifotides HT, Bose P, Verstovsek S. J Hematol Oncol. 2022;15(1):7. Publication license: https://creativecommons.org/licenses/by/4.0/.](https://ash.silverchair-cdn.com/ash/content_public/journal/blood/144/7/10.1182_blood.2023023719/2/blood_bld-2023-023719-c-gr1.jpeg?Expires=1761552765&Signature=Ix4xB4opgGJuPZyOtlMxKCM59OSDDkKznCIlJTpZa1pz-Zx5sc~HOQj64Z4r8GW0fO2rQDIzi2H3Ru5oUZJvDwsM2JbXZLUldILAlOKdoZ3JAzFYgQjFVjiq9zfVi0z~MRNZFxv3RCnGiZqK2uq-~yWxlzKU3wQ1AsQ598AU4CU3SENMJRS8Rm~vr4kvX5zU6tvft-BZPjx9l-MAyMwWn6vmycJgPT9oJG1QDZQXvV9ZSVRsJ1eIH7aalYjjNd6NoVapuj9XFmj2sOB9SLv~TEVABiuhRG2WdkRPvHwb6~6QWUbO6PUkAEQaCvLy4Ub5OKns-QX3Ix9kN5bVSr-Ogw__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA)
Systemic iron homeostasis and its regulation by the hepcidin-ferroportin axis. Momelotinib suppresses hepcidin expression in the liver via inhibition of the bone morphogenetic protein (BMP) 6/activin A receptor type 1 (ACVR1)/small mothers against decapentaplegic (SMAD) and interleukin 6 (IL-6)/JAK/STAT3 pathways, leading to reduced sequestration of iron in the reticuloendothelial system and enhanced iron availability for bone marrow erythropoiesis. Hepcidin is elevated in patients with MF due to aberrant hyperactivation of signaling via the BMP6-stimulated kinase, ACVR1/ALK2, and inflammatory cytokine signaling via IL-6, which is also elevated in patients with MF. Suppression of hepcidin expression in the liver increases circulating iron (transferrin [Tf]-Fe3+]2) and hemoglobin and stimulates erythropoiesis in the bone marrow. The lower panel lists the major causes of anemia in myelofibrosis. EPO, erythropoietin; ERFE, erythroferrone; H, hepcidin; MMB, momelotinib; RBC, red blood cell. Modified, with permission, from Chifotides HT, Bose P, Verstovsek S. J Hematol Oncol. 2022;15(1):7. Publication license: https://creativecommons.org/licenses/by/4.0/.
