hematology and oncology
Primary Myelofibrosis (PMF)
Pathophysiology of Primary Myelofibrosis
Myelofibrosis is a reactive, reversible increase in bone marrow collagen often with extramedullary hematopoiesis (primarily in the spleen). Myelofibrosis may be Primary (more common) Secondary to a number of hematologic, malignant, and nonmalignant conditions (see table) Primary myelofibrosis results from neoplastic transformation of a pluripotent hematopoietic stem cell. The primary myelofibrosis progeny cells stimulate bone marrow fibroblasts (which are not part of the neoplastic transformation) to produce excessive collagen. The peak incidence of primary myelofibrosis is between 50 and 70 years, and it occurs predominantly in males. Mutations of the Janus kinase 2 (JAK2) gene are present in a high proportion of cases of primary myelofibrosis. JAK2 is a member of the class I type tyrosine kinase family of enzymes and is involved in signal transduction forerythropoietin, thrombopoietin, and granulocyte colony-stimulating factor (G-CSF) receptors among other entities. Mutations of the thrombopoietin receptor gene (MPL) or the calreticulin (CALR) gene also may be the cause of primary myelofibrosis. However, there are rare cases of primary myelofibrosis in which none of these three mutations are present (triple-negative primary myelofibrosis). Some of these patients have other uncommonMPLmutations, which can only be detected by next generation sequencing. In primary myelofibrosis, nucleated red blood cells (normoblasts) and myelocytes are released into the circulation (leukoerythroblastosis) when there is extramedullary hematopoiesis (ie, non-marrow organs have taken over blood cell production because of marrow fibrosis ). The serum lactate dehydrogenase level is often elevated. Bone marrow failure eventually occurs, with consequent anemia and thrombocytopenia. Rapidly progressive, chemotherapy-incurable Overview of Leukemia develops in about 30% of patients. Malignant myelofibrosis (sometimes called acute myelofibrosis), is a rare variant of myelofibrosis characterized by pancytopenia, myeloblastosis, and marrow fibrosis that has a more rapidly progressive downhill course and is generally due to a type of acute leukemia called acute megakaryoblastic leukemia. 