ABSTRACT
The chronic myeloproliferative disorders include chronic myeloid leukemia (CML), essential thrombocythemia (ET), polycythemia vera (PV), and idiopathic myelofibrosis (IMF). Each disorder is a clonal hematological malignancy originating at the pluripotent hematopoietic stem cell level. These clonal hematopoietic disorders are characterized by proliferation of one or more of the myeloid (granulocytic, erythroid, and megakaryocytic) lineages. While in ET and PV, a relative normal blood production exists, this proliferation results in an increased number of granulocytes, red blood cells, and/or platelets. In contrast, advanced IMF is associated with ineffective hematopoiesis leading to cytopenia. Both ET and PV are usually associated with a prolonged clinical course, and with appropriate treatment, patients often survive for > 15 years. 1,2 In contrast, IMF has a more serious prognosis with a median survival of approximately 5 years. 3,4 IMF is characterized by cytopenia, megakaryocytic hyperplasia, splenomegaly, extramedullary hematopoiesis, and a leukoerythroblastic blood picture. The bone marrow histology shows fibrosis and increased angiogenesis. A number of agents, including erythropoietin, thalidomide, lenalidomide, hydroxyurea, melphalan, and busulfan, have been used to correct cytopenia or reduce splenomegaly. However, no drug has been shown to alter the natural course of the disease. The recent discovery of mutation of the Janus kinase 2 (JAK2) 5 and the thrombopoietin-receptor (MPL) 6 has resulted in activity towards
development of inhibitors, which might be used as non-toxic specific agents for treatment of BCR-ABL-negative myeloproliferative disorders. Currently allogeneic stem cell transplantation is the only curative treatment approach in IMF.
