Patients with splenomegaly and systemic symptoms are eligible for therapy with ruxolitinib, a JAK1/2 inhibitor that suppresses clonal myeloproliferation and release of proinflammatory cytokines, reducing splenomegaly and constitutional symptoms in around 50% of patients, without inducing significant reductions in mutation load/marrow fibrosis. Here, JAK1 is linked to Splenomegaly.