Myelofibrosis (MF) is a BCR-ABL1-negative myeloproliferative
neoplasm characterized by clonal myeloproliferation, dysregulated
kinase signaling, and release of abnormal
cytokines. In recent years, important progress has been made in the knowledge of the molecular biology and the prognostic assessment of MF. Conventional treatment has limited impact on the patients' survival; it includes a wait-and-see approach for asymptomatic patients,
erythropoiesis-stimulating agents,
androgens, or
immunomodulatory agents for
anemia, cytoreductive drugs such as
hydroxyurea for the
splenomegaly and constitutional symptoms, and
splenectomy or
radiotherapy in selected patients. The discovery of the
Janus kinase (JAK)2 mutation triggered the development of
molecular targeted therapy of MF. The
JAK inhibitors are effective in both JAK2-positive and JAK2-negative MF; one of them,
ruxolitinib, is the current best available
therapy for MF
splenomegaly and constitutional symptoms. However, although
ruxolitinib has changed the therapeutic scenario of MF, there is no clear indication of a disease-modifying effect. Allogeneic
stem cell transplantation remains the only curative
therapy of MF, but due to its associated morbidity and mortality, it is usually restricted to eligible high- and intermediate-2-risk MF patients. To improve current therapeutic results, the combination of
JAK inhibitors with other agents is currently being tested, and newer drugs are being investigated.