- Clinical science
Myeloproliferative neoplasms (MPN) are a group of disorders characterized by a proliferation of malignant hematopoietic stem cells that belong to the myeloid cell lineage. The most clinically relevant MPN include chronic myeloid leukemia (CML), polycythemia vera (PV), primary myelofibrosis (PMF), and essential thrombocythemia (ET). An important etiological factor is the mutation of the Janus kinase-2 (JAK2) gene, which is present in almost all cases of PV and in approximately 50% of patients with ET and PMF. In contrast to the other subtypes, CML is characterized by a distinct translocation between chromosome 9 and 22 (BCR-ABL1 fusion gene). Each of these neoplasms has a typical pattern of cell proliferation: granulocytes are increased in CML, thrombocytes in ET, and all cell lines show increased proliferation in PV. PMF, on the other hand, shows an initial hyperproliferative phase, but eventually progresses to pancytopenia. All myeloproliferative neoplasms may lead to elevated uric acid levels and gout as a result of increased cellular breakdown. They are also associated with an increased risk of . Treatment involves to reduce the cell count, polychemotherapy to halt the proliferation of malignant cells, and, in young patients, allogeneic stem cell transplantation.
According to the WHO classification, the following disorders belong to the group of myeloproliferative neoplasms:
With the exception of CML, all of these disorders show varying degrees of JAK2 mutations, which can be used as a diagnostic marker. The mutation causes the exchange of two amino acids (valine → phenylalanine), which, in turn, results in dysregulation of the tyrosine kinase JAK2.
- Description: : any myeloproliferative neoplasm leading to bone marrow fibrosis, extramedullary hematopoiesis, and splenomegaly.
- Epidemiology: : peak incidence between age 60–70 years
- Etiology: unknown
- Genetics: JAK2 mutation in 50% of cases
- Weakness, fatigue, weight loss
- Splenomegaly: left upper quadrant abdominal pain
- Hyperproliferative phase (early phase): thrombocytosis (→ thromboembolic events) and leukocytosis
- Pancytopenic phase (late phase):
- Laboratory studies: ↑ leukocyte alkaline phosphatase; , LDH, and uric acid
- Peripheral blood smear: dacrocytes (teardrop cells)
- Bone marrow aspiration: punctio sicca
- Curative: allogeneic stem cell transplantation; (option for younger patients)
- 50% asymptomatic
- Thromboembolic events
- Increased risk of fetal loss
- Vasomotor symptoms (headache, visual disturbances, acral paresthesias)
- Petechial bleeding
ET is a diagnosis of exclusion; all other causes of thrombocytosis must be ruled out before the diagnosis can be made.
- Thrombocytosis (> 600,000/μL)
- ↑ LDH and uric acid
- Bone marrow aspiration: hyperplasia of megakaryocytes
- Reactive thrombocytosis: platelet proliferate as a reaction to a certain condition, and not because of an intrinsic defect
- Prevent thromboembolisms; : low dose aspirin
- Reduce thrombocyte count: hydroxyurea or interferon alpha
- Description: leukemia with monoclonal proliferation of eosinophilic granulocytes, that causes peripheral eosinophilia and tissue damage
- Clinical features