From palliation to epigenetic therapy in myelofibrosis

Myelofibrosis shows a progressive clinical course and usually a poor, lethal prognosis. The molecular pathogenesis of this disease largely remains to be fully understood but the identification of the JAK2V617F mutation in more than half of patients was a major improvement in our understanding of the disease biology and may represent the first biologic marker useful for risk stratification, independently from conventional clinical predictors. After many elusive efforts, new effective treatment strategies are becoming available for this disease. Allogeneic transplantation following reduced-intensity conditioning programs, at least in some patients, may induce not only a hematologic response but also a molecular remission, thus supporting the hope of a possible, definitive eradication of the disease. Moreover, new innovative drugs, targeting either the JAK2V617F mutation or more general oncogenic mechanisms, may provide widely applicable, effective treatments to many patients for whom allogeneic transplantation is not feasible.