Figure 1.

Pathophysiological characteristics of PMF. Primary myelofibrosis is characterized by a clonal amplification of hematopoietic stem cells (HSCs) and a prominent proliferation of "dystrophic" megakaryocytes (MK) that partly result from the presence of gain-of-function mutations involving JAK2 and MPL genes and that is associated with a migration of HSC from bone marrow (BM) to spleen and liver through peripheral blood (PB). Such myeloproliferation is associated with alterations of stroma featured by a myelofibrosis, an osteosclerosis and a neoangiogenesis. This stromal reaction is reported to be secondary to the stimulation of stromal cells including fibroblasts, osteoblasts and endothelial cells by growth factors (GFs) produced in excess by cells from the hematopoietic clone and especially by MK cells.