General Information About Chronic Myeloproliferative Neoplasms (MPN)
The chronic MPN consist of chronic myelogenous leukemia, polycythemia vera (p. vera), primary myelofibrosis, essential thrombocythemia, chronic neutrophilic leukemia, and chronic eosinophilic leukemia. All of these disorders involve dysregulation at the multipotent hematopoietic stem cell (CD34), with one or more of the following shared features:
- Overproduction of one or several blood elements with dominance of a transformed clone.
- Hypercellular marrow/marrow fibrosis.
- Cytogenetic abnormalities.
- Thrombotic and/or hemorrhagic diatheses.
- Extramedullary hematopoiesis (liver/spleen).
- Transformation to acute leukemia.
- Overlapping clinical features.
Chronic MPNs usually occur sporadically; however, familial clusters of MPNs have been reported. These familial clusters include autosomal-dominant inheritance and autosomal-recessive inheritance. Patients with p. vera and essential thrombocythemia have marked increases of red blood cell and platelet production, respectively. Treatment is directed at reducing the excessive numbers of blood cells. Both p. vera and essential thrombocythemia can develop a spent phase late in their courses that resembles primary myelofibrosis with cytopenias and marrow hypoplasia and fibrosis.[2-4] A specific point mutation in one copy of the Janus kinase 2 gene (JAK2), a cytoplasmic tyrosine kinase, on chromosome 9, which causes increased proliferation and survival of hematopoietic precursors in vitro, has been identified in most patients with p. vera, essential thrombocythemia, and idiopathic myelofibrosis.[5-10] Researchers are pursuing specific targeting of this aberrant protein.
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