Figure 4.

PMF; the "Bad Seeds in Bad Soil" model. In PMF, whereas the initial molecular defect at the origin of the hematopoietic clone is still unknown, altered interactions between CD34⁺ HSCs and stromal cells in the medullar environment would result in an increased cytokine production by the clonal hematopoietic cells and especially by dystrophic megakaryocytes and monocytes. Production in excess of hematopoietic, fibrogenic, and angiogenic growth factors would stimulate myelofibrosis, osteosclerosis and angiogenesis through activation of stromal and endothelial cells. Consequently, by acquiring new properties, stromal cells would create a pathological microenvironment that participates in the development and maintenance of the hematopoietic clone. Mk: Megakaryocytes; Mo: Monocytes; Ne: Neutrophiles; Ob: Osteoblasts; Oc: osteoclasts; Fb: Fibroblasts.