Stem cells moving from bone marrow to spleen/liver niches in PMF. As a consequence of a still unknown molecular event, clonal hematopoietic stem cells proliferate and generate differentiated cells, resulting in the medullar hyperproliferative stage described in early disease. Among these cells, dystrophic megakaryocytes produce or release several growth factors and proteases within the bone marrow environment, leading to myelofibrosis and to an imbalance between endosteal and vascular niches. This imbalance would favor proliferation of stem cells (SCs) including hematopoietic, endothelial, and likely mesenchymal stem cells (HSCs, ESCs, and MSCs, respectively) and their mobilization through blood, resulting in a higher number of circulating SCs and in a terminal bone marrow aplasia. These SCs colonize the spleen in which newly created or reinitialized vascular niches would favor their homing and differentiation, leading to the splenomegaly/hepatomegaly that characterizes PMF.