JAK3 and Splenomegaly: Ruxolitinib, which inhibits JAK2 but also TYK2, JAK1 and JAK3 10 at similar degrees demonstrated durable reduction in splenomegaly and constitutional symptoms with improved quality of life in comparison to placebo-controlled 21 or best available therapy 22 in phase 3 trials and an impact on survival for patients originally randomized to ruxolitinib compared with those originally randomized to placebo in both COMFORT trials 23.