Myelofibrosis - diagnosis, management, new treatment options

Of the myeloproliferative neoplasm (MPN), myelofibrosis (MF) is associated with the greatest symptom burden and poorest prognosis and is characterized by constitutional symptoms, cytopenias, splenomegaly and bone marrow fibrosis. A hallmark of MF is dysregulation of the Janus kinase/signal transducer and activator of transcription pathway the led to the development of JAK inhibitors targeting this pathway. Calreticulin gene mutations have recently been identified in JAK 2 mutation negative patients. Identification of JAK inhibitor resistance and broad contributors to MF disease pathogenesis from epigenetic deregulators, pathways that work in concert with JAKSTAT, mTOR/AKT, PI3K, RAS/RAF/MEK, telo merase inhibitor, fibrosis-promoting factors and the MF megakaryocyt should be partners with JAK inhibitors in therapy of MF. (author)