JAK2 and Splenomegaly: Regulatory approval of the oral JAK1/JAK2 inhibitor ruxolitinib (Quintás-Cardama et al., 2010) was based on the randomized, open-label, multicenter phase III RESPONSE trial, which evaluated ruxolitinib vs. best available therapy (BAT; i.e., hydroxyurea, interferon-α, anagrelide, immunomodulators, pipobroman, and observation alone) in patients with PV who required phlebotomy to control hematocrit, had splenomegaly, and were resistant to or intolerant of hydroxyurea (Vannucchi et al., 2015).