Myeloproliferative neoplasms: Polycythemia vera, Essential thrombocytosis, Idiopathic myelofibrosis (Myeloproliferative neoplasms: polycythemia vera, with essential thrombocythemia, myelofibrosis primary) - Gen JAK2
Myeloproliferative neoplasms, until 2008 called "chronic myeloproliferative disorders" are a chronic hematological processes derived from a hematopoietic stem cell mutant. Chronic myeloid leukemia is a myeloproliferative neoplasia but, unlike the others, is characterized by a translocation between chromosome 9 and 22, resulting in the familiar Philadelphia chromosome and bcr-abl protein - see Chronic myelogenous leukemia. Treatment with imatinib. BCR-abl gene. Among the myeloproliferative neoplasms caused by a somatic mutation in JAK2 three major categories that share many characteristics with each other are different: - see Polycythemia vera, JAK2 and TET2 genes -, essential thrombocytosis (ET) - polycythemia vera (PV) see Thrombocytosis essential, CALR, JAK2, MPL, TET2, THPO genes - and idiopathic myelofibrosis (MI), also known latter as myeloid metaplasia with myelofibrosis or primary myelofibrosis - see idiopathic myelofibrosis, JAK2, MPL, CALR and TET2 genes -.
These processes are characterized by a hyperactive hematopoiesis due to activating mutations, inducing increased production of red cells and platelets, the main characteristics of polycythemia vera and essential thrombocytosis respectively. The main clinical complication in these processes is thrombosis and less bleeding can also occur. In the longer term, some patients may develop myelofibrosis or acute myeloid leukemia. The last stage of idiopathic myelofibrosis is characterized by fibrosis of the bone marrow cytopenia and splenomegaly and can also become acute myelogenous leukemia.
The Val617Phe or V617F mutation which generates a valine substitution by a felinananina in position 617, is located in exon 14 of the JAK2 gene has been found in approximately 96% of patients with polycythemia vera, in the 50- 60% of patients with essential thrombocytosis and approximately 50% of those affected by primary myelofibrosis. However, in some patients who other genetic alterations this mutation in exon 12 of this same gene (delF537-K539, K539L, delN542-E543) were found.
The JAK2 gene is located on the short arm of chromosome 9 (9p24), it is composed of 25 exons although genetic abnormalities generating myeloproliferative disorders are focused into two, 12 and 14- encoding a tyrosine kinase with a role key signal transduction multiple recipients hematopoietic growth factors. The above described mutations exert an activating role on the JAK2 gene, because they are located on the JH2 domain that negatively regulates the activity of the kinase domain (JH1).
Most mutations in JAK2 not inherited, but are associated with somatic genetic changes, which means that are acquired during the life of a person and are present only in certain cells.
Tests in IVAMI: in IVAMI perform detection of mutations associated with the development of myeloproliferative neoplasms, by complete PCR amplification of the exons of the JAK2 gene, and subsequent sequencing. It is recommended to begin the study by exon 14, where most genetic defects are confined and, if negative, the study of exon 12, where there have been other mutations associated with these processes is suggested.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).