Precision medicine in myelofibrosis: from molecular profiling to personalized therapy.

Precision medicine in myelofibrosis (MF) has moved beyond confirmation of a driver mutation toward an integrated interpretation of marrow morphology, molecular profile, cytogenetics, clinical phenotype, symptom burden, and transplant fitness. Myelofibrosis is biologically heterogeneous across both primary MF and secondary MF arising after polycythemia vera or essential thrombocythemia, with clinically relevant differences in disease origin, driver distribution, prognostic model validation, phenotype, and outcome. Several prognostic tools and much of the strongest molecular-risk evidence remain best validated in primary MF cohorts; therefore, PMF-derived molecular signals should be applied cautiously to secondary MF, where MYSEC-PM and disease-origin-specific interpretation are more appropriate. Current precision care is actionable now in diagnosis, integrated risk assessment, phenotype-adapted JAK inhibitor selection, structured symptom assessment, and transplant timing. Ruxolitinib remains the anchor first-line option for symptomatic proliferative disease; fedratinib provides an alternative or post-ruxolitinib option in selected patients with preserved platelet reserve; pacritinib is particularly relevant in severe thrombocytopenia; and momelotinib has a differentiated role in anemia-dominant MF. Allogeneic hematopoietic cell transplantation remains the only curative strategy and should be discussed early for biologically or clinically high-risk disease. Emerging artificial intelligence (AI) applications in digital pathology, prognostic modeling, and post-transplant prediction may further operationalize precision care, but they remain adjunctive rather than autonomous and require external validation, explainability, governance, and human oversight before routine deployment. This review reframes MF through an MF-specific precision-medicine lens centered on biology, patient selection, phenotype-adapted treatment, transplantation, monitoring, and the boundary between what is currently actionable and what remains investigational.