Pathogenesis of myelofibrosis: role of ineffective megakaryopoiesis and megakaryocyte components.

The pathological and ultrastructural features of the bone marrow and the kinetics of megakaryopoiesis in patients with primary myelofibrosis indicate that a vast number of developing megakaryocytes die within the bone marrow (ineffective megakaryopoiesis). This leads to an excessive concentration of megakaryocyte intracytoplasmic components in the marrow intercellular space. Current concepts of marrow collagen regulation and megakaryocyte composition lend support to the hypothesis advocating that the development of marrow fibrosis involves two megakaryocyte components: growth factor and factor 4. The growth factor stimulates fibroblast proliferation and collagen secretion while factor 4 inhibits the activity of the enzyme collagenase. The imbalance between increased collagen production and decreased collagen degradation results in an excessive deposition of collagens in bone marrow matrix.