Myeloproliferative neoplasms are clonal proliferations of bone marrow stem cells, which can manifest as an increased number of 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
Polycythemia vera Polycythemia Vera Polycythemia vera (PV) is a chronic myeloproliferative neoplasm characterized by an increase in morphologically normal red cells (its hallmark), but also white cells and platelets. Ten to 30%... read more (some combination of increased WBCs, RBCs, and/or platelets)
Essential thrombocythemia, primary myelofibrosis, and polycythemia vera are Philadelphia chromosome–negative myeloproliferative neoplasms that can spontaneously transform to acute leukemia Acute leukemias Leukemia is a malignant condition involving the excess production of immature or abnormal leukocytes, which eventually suppresses the production of normal blood cells and results in symptoms... read more . Essential thrombocythemia and polycythemia vera transform at very low rates in the absence of prolonged exposure to chemotherapeutic agents.
Less common myeloproliferative neoplasms include the hypereosinophilic syndromes Hypereosinophilic Syndrome Hypereosinophilic syndrome is a condition characterized by peripheral blood eosinophilia with manifestations of organ system involvement or dysfunction directly related to eosinophilia in the... read more and mastocytosis Mastocytosis Mastocytosis is mast cell infiltration of skin or other tissues and organs. Symptoms result mainly from mediator release and include pruritus, flushing, and dyspepsia due to gastric hypersecretion... read more . Myeloproliferative neoplasms also can overlap with the myelodysplastic syndromes Myelodysplastic Syndrome (MDS) The myelodysplastic syndrome (MDS) is group of disorders typified by peripheral cytopenia, dysplastic hematopoietic progenitors, a hypercellular or hypocellular bone marrow, and a high risk... read more .
Each disorder is identified according to its predominant features (see table Classification of Myeloproliferative Neoplasms Classification of Myeloproliferative Neoplasms ). Overlap in of clinical and laboratory findings occurs because essential thrombocythemia. primary myelofibrosis, and polycythemia vera can have driver mutations that constitutively activate Janus kinase 2 (JAK2). Although proliferation of one or more hematopoietic cell types dominates the clinical picture in each of these disorders, all three are caused by clonal proliferation of a pluripotent hematopoietic stem cell, causing an increased proliferation of normal 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 Polycythemia Vera Polycythemia vera (PV) is a chronic myeloproliferative neoplasm characterized by an increase in morphologically normal red cells (its hallmark), but also white cells and platelets. Ten to 30%... read more .