Overview of Myeloproliferative Neoplasms
Myeloproliferative neoplasms are clonal proliferations of bone marrow stem cells, which can manifest as increased platelets, red blood cells (RBCs), or white blood cells (WBCs) in the circulation and sometimes as increased fibrosis in the bone marrow with consequent extramedullary hematopoiesis (cell production outside the marrow). Based on these abnormalities, they are classified as
Essential thrombocythemia, primary myelofibrosis, and polycythemia vera are Philadelphia chromosome–negative myeloproliferative neoplasms that can spontaneously transform to acute leukemia.
Each disorder is identified according to its predominant feature or site of proliferation (see table Classification of Myeloproliferative Neoplasms). Despite overlap, each disorder has a somewhat typical constellation of clinical features, laboratory findings, and course. Although proliferation of one cell line may dominate the clinical picture, each disorder is caused by clonal proliferation of a pluripotent stem cell, causing varying degrees of abnormal proliferation of RBC, WBC, and platelet progenitors in the bone marrow. This abnormal clone does not, however, produce bone marrow fibroblasts, which can proliferate in a polyclonal reactive fashion in response to the abnormal stem cell.
Mutations of the Janus kinase 2 ( JAK2) gene are responsible for polycythemia vera and a high proportion of cases of essential thrombocythemia and primary myelofibrosis. Janus kinase 2 is a member of the tyrosine kinase family of enzymes and is involved in signal transduction for erythropoietin, thrombopoietin, and granulocyte colony-stimulating factor (G-CSF) among other entities. The thrombopoietin receptor gene (MPL) or the calreticulin (CALR) gene is also mutated in a significant proportion of essential thrombocythemia and primary myelofibrosis patients and rarely in polycythemia vera.