Загальні відомості про мієлопроліферативні захворювання

Myeloproliferative neoplasms are clonal proliferations of bone marrow hematopoietic stem cells, which can manifest as an increased number of functionally normal 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

• Essential thrombocythemia (increased platelets)

• Primary myelofibrosis (marrow fibrosis or scarring)

• Polycythemia vera (any combination of increased WBCs, RBCs, and platelets but rarely erythrocytosis alone)

• Chronic myeloid leukemia (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. Essential thrombocythemia and polycythemia vera transform to acute leukemia at very low rates in the absence of prolonged exposure to chemotherapeutic agents such as hydroxyurea.

Less common myeloproliferative neoplasms include the hypereosinophilic syndromes and mastocytosis. Myeloproliferative neoplasms also can overlap with the myelodysplastic syndromes.

Each disorder is identified according to its predominant features (see table Classification of Myeloproliferative Neoplasms). Although proliferation of one or more hematopoietic cell types dominates the clinical picture in each of these disorders, all 3 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 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.