Targeted treatment of anemia in myelofibrosis and the impact of JAK inhibitors

INTRODUCTION: Anemia is a hallmark feature of Myelofibrosis (MF), frequently present at diagnosis and almost universal with disease evolution. It is a major contributor to symptom burden, transfusion dependence, healthcare utilization, and adverse prognosis, and is incorporated into contemporary risk stratification models. AREAS COVERED: This review highlights current definitions of MF-associated anemia, including trial and prognostic thresholds, and outlines its incidence, clinical impact, and multifactorial pathophysiology. Therapeutic approaches reviewed include supportive options, differential anemia profiles of JAK inhibitors and emerging targeted strategies like TGF-β ligand traps, hepcidin-pathway modulation, novel agents and combination approaches. EXPERT OPINION: Anemia in MF is a core feature, not just a complication. The shift is from supportive to mechanism-guided therapy targeting iron restriction, erythroid maturation, inflammation, and newer JAK inhibitors with anemia benefits as well as mutation targeted therapy. Unmet needs include standardized endpoints, biologically stratified trials, and validation of hemoglobin and transfusion responses as markers. Strategies like momelotinib plus luspatercept, earlier intervention, and new molecular therapies could turn treatment from palliation to durable control and disease modification.