{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T12:22:29Z","timestamp":1789734149753,"version":"4.0.1"},"reference-count":102,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,12,28]],"date-time":"2023-12-28T00:00:00Z","timestamp":1703721600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Cancer Institute (National Institutes of Health)","award":["P30 CA016672"],"award-info":[{"award-number":["P30 CA016672"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Activin receptor type I (ACVR1) is a transmembrane kinase receptor belonging to bone morphogenic protein receptors (BMPs). ACVR1 plays an important role in hematopoiesis and anemia via the BMP6\/ACVR1\/SMAD pathway, which regulates expression of hepcidin, the master regulator of iron homeostasis. Elevated hepcidin levels are inversely associated with plasma iron levels, and chronic hepcidin expression leads to iron-restricted anemia. Anemia is one of the hallmarks of myelofibrosis (MF), a bone marrow (BM) malignancy characterized by BM scarring resulting in impaired hematopoiesis, splenomegaly, and systemic symptoms. Anemia and red blood cell transfusions negatively impact MF prognosis. Among the approved JAK inhibitors (ruxolitinib, fedratinib, momelotinib, and pacritinib) for MF, momelotinib and pacritinib are preferably used in cytopenic patients; both agents are potent ACVR1 inhibitors that suppress hepcidin expression via the BMP6\/ACVR1\/SMAD pathway and restore iron homeostasis\/erythropoiesis. In September 2023, momelotinib was approved as a treatment for patients with MF and anemia. Zilurgisertib (ACVR1 inhibitor) and DISC-0974 (anti-hemojuvelin monoclonal antibody) are evaluated in early phase clinical trials in patients with MF and anemia. Luspatercept (ACVR2B ligand trap) is assessed in transfusion-dependent MF patients in a registrational phase 3 trial. Approved ACVR1 inhibitors and novel agents in development are poised to improve the outcomes of anemic MF patients.<\/jats:p>","DOI":"10.3390\/cancers16010154","type":"journal-article","created":{"date-parts":[[2023,12,28]],"date-time":"2023-12-28T09:35:21Z","timestamp":1703756121000},"page":"154","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["ACVR1: A Novel Therapeutic Target to Treat Anemia in Myelofibrosis"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9510-4755","authenticated-orcid":false,"given":"Andrea","family":"Duminuco","sequence":"first","affiliation":[{"name":"Hematology Unit with BMT, A.O.U. Policlinico \u201cG.Rodolico-San Marco\u201d, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8044-4960","authenticated-orcid":false,"given":"Helen T.","family":"Chifotides","sequence":"additional","affiliation":[{"name":"Department of Leukemia, The University of Texas MD Anderson Cancer Center, 1400 Holcombe Blvd., Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5047-7515","authenticated-orcid":false,"given":"Sebastiano","family":"Giallongo","sequence":"additional","affiliation":[{"name":"Department of Medical, Surgical Sciences and Advanced Technologies \u201cG.F. Ingrassia\u201d, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cesarina","family":"Giallongo","sequence":"additional","affiliation":[{"name":"Department of Medical, Surgical Sciences and Advanced Technologies \u201cG.F. Ingrassia\u201d, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4416-8556","authenticated-orcid":false,"given":"Daniele","family":"Tibullo","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1859-6319","authenticated-orcid":false,"given":"Giuseppe A.","family":"Palumbo","sequence":"additional","affiliation":[{"name":"Hematology Unit with BMT, A.O.U. Policlinico \u201cG.Rodolico-San Marco\u201d, 95123 Catania, Italy"},{"name":"Department of Medical, Surgical Sciences and Advanced Technologies \u201cG.F. Ingrassia\u201d, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1038\/s41375-019-0420-1","article-title":"The role of TGF\u03b2 in hematopoiesis and myeloid disorders","volume":"33","author":"Bataller","year":"2019","journal-title":"Leukemia"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Katagiri, T., Tsukamoto, S., and Kuratani, M. (2021). Accumulated Knowledge of Activin Receptor-Like Kinase 2 (ALK2)\/Activin A Receptor, Type 1 (ACVR1) as a Target for Human Disorders. Biomedicines, 9.","DOI":"10.3390\/biomedicines9070736"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Valer, J.A., S\u00e1nchez-De-Diego, C., Pimenta-Lopes, C., Rosa, J.L., and Ventura, F. (2019). ACVR1 Function in Health and Disease. 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