Moreover, MEK1/2 and ERK1/2 activation overcomes JAK1/2 inhibition in vivo in MPN mouse models and the administration of MEK1/2 or ERK1/2 inhibitors in combination with Ruxolitinib displayed superior therapeutic efficacy in vivo by reducing splenomegaly, disease burden and myelofibrosis [24, 25]. This evidence concerns the gene MAP2K1 and Splenomegaly.