[The chronic Philadelphia chromosome-negative myeloproliferative syndrome I. Pathogenesis and pathophysiology]

In polycythaemia vera (PV) the erythroid progenitors proliferate autonomously independently of the circulating erythropoietin. The progenitors are hypersensitive to various growth factors, including insulin-like growth factor 1, which inhibits apoptosis in erythroid and myeloid progenitor cells. No change has been found in the erythropoietin (EPO) receptor. Thrombopoietin (Tpo) regulates the production of haematopoietic progenitor cells, particularly of platelets. By inhibiting apoptosis, this growth factor may be responsible for the autonomous proliferation of the megakaryocyte cell lineage in PV and idiopathic myelofibrosis (IMF), which are featured by highly elevated circulating Tpo levels. Thrombopoietin may also be involved in the pathogenesis of myelofibrosis and development of extramedullary haematopoiesis. Both fibrogenesis and angiogenesis in the bone marrow, spleen, and liver develop secondary to the release of various growth-promoting factors from the megakaryocyte cell lineage. The lesion of the pluripotent stem cell in PV and IMF seems to imply several defects, including lack of or decreased expression of the Tpo receptor, alterations in the sensitivity of progenitor cells to various growth factors, and alterations in important gene systems (Bcl-2), which govern cell survival. Essential thrombocytosis seems to be a heterogeneous disease entity, as about 50% of the patients have polyclonal haematopoiesis.