Molecular Pathogenesis of Chronic MPDs

Chronic myeloproliferative disorders (MPDs), first proposed by Dameshek in 1951, are clonal hematopoietic stem cell disorders characterized by proliferation of 1 or more myeloid cell lineages in the bone marrow and increased numbers of mature and immature cells in peripheral blood.1 According to the World Health Organization classification, MPDs include polycythemia vera (PV), essential thrombocythemia (ET), idiopathic myelofibrosis (IMF) and chronic myeloid leukemia (CML), plus rarer subtypes such as chronic neutrophilic leukemia, hypereosinophilic syndrome and chronic eosinophilic leukemia. These diseases overlap with myelodysplastic/myeloproliferative diseases such as atypical CML and chronic myelomonocytic leukemia, in which proliferation is accompanied by dysplastic features or ineffective hematopoiesis in other lineages.2 The clinical pictures of these disorders share many features: genesis in a single, multipotent hematopoietic stem cell that assumes dominance over nontransformed progenitors; hypercellularity of the marrow, with apparently unstimulated overproduction of 1 or more of the formed elements of blood; and increased risk of thrombosis and bleeding, spontaneous transformation to acute leukemia and marrow fibrosis.3