A limited number of studies on the use of JAK inhibitors in patients with myelofibrosis reported a dramatic decrease in the size of splenomegaly, but no significant improvement in leukocyte counts, anemia, number of platelets, and bone marrow fibrosis has been observed.[18,19,20] This incomplete resolution of signs and symptoms with JAK2 inhibition supports our view, i.e. JAK2V617F is not the only actor of the scene, there should be other molecular mechanisms and/or mutations which contribute to the development of fibrosis in the bone marrow of patients with MPNs. This evidence concerns the gene JAK2 and myelofibrosis.