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), alone or in combination, in the circulation and sometimes with fibrosis in the bone marrow and extramedullary hematopoiesis (cell production outside the marrow). Based on these abnormalities, they are classified as
Polycythemia vera Polycythemia Vera Polycythemia vera is a chronic myeloproliferative neoplasm characterized by an increase in morphologically normal red cells (its hallmark), but also white cells and platelets. Ten to 15% of... read more (any combination of increased WBCs, RBCs, and platelets but rarely erythrocytosis alone)
Chronic myeloid leukemia Chronic Myeloid Leukemia (CML) Chronic myeloid leukemia (CML) occurs when a pluripotent stem cell undergoes malignant transformation and clonal myeloproliferation, leading to a striking overproduction of mature and immature... read more (associated with the Philadelphia chromosome and expression of BCR/ABL fusion gene)
Essential thrombocythemia, primary myelofibrosis, and polycythemia vera 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 such as hydroxyurea.
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 and Mast Cell Activation Syndrome Mastocytosis is mast cell proliferation with infiltration of skin or other tissues and organs. Mast cell activation syndrome is increased and inappropriate activation of mast cells without clonal... read more . Myeloproliferative neoplasms also can overlap with the myelodysplastic syndromes Myelodysplastic Syndrome (MDS) The myelodysplastic syndrome (MDS) is group of clonal hematopoietic stem cell disorders typified by peripheral cytopenia, dysplastic hematopoietic progenitors, a hypercellular or hypocellular... read more .
Each disorder is identified according to its predominant features (see table Classification of Myeloproliferative Neoplasms Classification of Myeloproliferative Neoplasms ). 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, and reversible fashion in response to the abnormal stem cell.
Overlap in of clinical and laboratory findings occurs because of a common etiology. 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 type I tyrosine kinase family of enzymes and is involved in signal transduction for the erythropoietin, thrombopoietin, and granulocyte colony-stimulating factor (G-CSF) receptors. 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 is a chronic myeloproliferative neoplasm characterized by an increase in morphologically normal red cells (its hallmark), but also white cells and platelets. Ten to 15% of... read more .
Classification of Myeloproliferative Neoplasms
Sometimes leading to bone marrow fibrosis
Anemia, leukocytosis, thrombocytosis, and bone marrow fibrosis with extramedullary hematopoiesis
Erythrocytosis usually with concurrent increased WBC and platelet counts and sometimes extramedullary hematopoiesis
Granulocytosis and thrombocytosis
Tremblay D, Yacoub A, Hoffman R: Overview of myeloproliferative neoplasms. Hematol Oncol Clin N Am 35 :159-176, 2021. doi: 10.1016/j.hoc.2020.12.001