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Current management of anemia is challenged by limited approved drugs that specifically treat anemia in myelofibrosis (MF) and myelodysplastic syndrome (MDS). Newer therapies target the transforming growth factor beta (TGF\u2010\u03b2)\u2010bone morphogenic protein\/sons of mothers against decapentaplegic (BMP\u2010SMAD) signaling pathway, which plays a significant role in ineffective erythropoiesis (SMAD 2\/3) and abnormal hepcidin production (SMAD 1\/5\/8). These include TGF\u2010\u03b2 ligand traps (luspatercept, elritercept), activin A receptor type 1 (ACVR1)\/activin receptor\u2010like kinase 2 (ALK2) inhibitors (momelotinib, zilurgisertib), and anti\u2010hemojuvelin antibody\u2010based therapies (DISC\u20100974). Luspatercept and momelotinib are approved for anemia related to lower\u2010risk MDS and MF, respectively, and represent an important addition to the treatment armamentarium, along with imetelstat, a telomerase inhibitor, recently ratified for anemia in lower\u2010risk MDS. A promising strategy to overcome the limitations of existing anemia\u2010directed therapies includes the use of drug combinations with complementary mechanisms (luspatercept\u2009+\u2009erythropoiesis stimulating agents, luspatercept\u2009+\u2009momelotinib, DISC\u20100974\u2009+\u2009momelotinib), and harnessing the erythropoietic potential of sodium\u2010glucose co\u2010transporter\u20102 inhibitors (SGLT\u20102I). Future research should address the complex pathophysiology of anemia, standardize definitions for anemia with gender\u2010specified cutoffs, implement uniform erythroid response criteria, and consider early therapeutic intervention in clinical trials for anemia\u2010directed therapies.<\/jats:p>","DOI":"10.1002\/ajh.27659","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T21:04:04Z","timestamp":1741727044000},"page":"51-65","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Emerging Pathogenetic Mechanisms and New Drugs for Anemia in Myelofibrosis and Myelodysplastic Syndromes"],"prefix":"10.1002","volume":"100","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9104-6172","authenticated-orcid":false,"given":"Naseema","family":"Gangat","sequence":"first","affiliation":[{"name":"Division of Hematology Mayo Clinic  Rochester Minnesota 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