A Journey Through JAK Inhibitors for the Treatment of Myeloproliferative Diseases

Purpose of ReviewChronic myeloproliferative neoplasms (MPN) represent a group of diseases characterised by constitutive activation of the JAK/STAT pathway in a clonal myeloid precursor. The therapeutic approach aims to treat the symptom burden (headache, itching, debilitation), splenomegaly, slow down the fibrotic proliferation in the bone marrow and reduce the risk of thrombosis/bleeding whilst avoiding leukaemic transformation.Recent FindingsIn recent years, the advent of JAK inhibitors (JAKi) has significantly broadened treatment options for these patients. In myelofibrosis, symptom control and splenomegaly reduction can improve quality of life with improved overall survival, not impacting progression into acute leukaemia. Several JAKi are available and used worldwide, and combination approaches are now being explored.In this chapter, we review the approved JAKi, highlighting its strengths, exploring potential guidelines in choosing which one to use and reasoning towards future perspectives, where the combinations of therapies seem to promise the best results.