Essential thrombocytosis -Trombocitemia essentially (Essential thrombocythemia) - Genes CALR, JAK2, MPL, TET2 and THPO.  

Essential thrombocythemia is a disorder characterized by increased platelet count. While some people with this condition have no symptoms, others develop problems associated with excess platelets. Thrombosis is common in people with this disorder, causing many of the signs and symptoms of it. Clots which block blood flow to the brain can cause strokes or transient ischemic attacks. Thrombosis can cause pulmonary embolism and dyspnea. Another symptom is abnormal bleeding, which occurs most often in people with very high platelet number. Affected individuals may have nosebleeds, bleeding gums, or gastrointestinal bleeding. Other signs and symptoms include splenomegaly essential thrombocythemia, weakness, headaches or feeling skin burns, paresthesia or itching. Some people have episodes of severe pain, redness and erythromelalgia, which usually occur on the hands and feet.

This process is due to mutations in the CALR, JAK2, MPL, TET2 and THPO genes being CALR and JAK2 the   They are having mutations more frequently.

The CALR gene, located on the short arm of chromosome 19 (19p13.3-p13.2) encoding calreticulin protein. This protein is found in various parts of the cell, including the endoplasmic reticulum inside (ER), cytoplasm, and on the outer surface of the cell. The endoplasmic reticulum is involved in the processing and transport of proteins, and in this structure, calreticulin ensures the proper folding of proteins newly formed. The RE is also a storage location for calcium ions, and calreticulin is involved in maintaining adequate calcium ion concentrations in this structure. Through the regulation of calcium and other mechanisms, it is believed that calreticulin exercises control of gene activity, proliferation and cell migration, adhesion, and apoptosis. The function of this protein is important for immune system function and wound healing. Somatic mutations in the gene CALR removed or added small amounts of genetic material to a region of exon 9 of this gene. These genetic changes lead to the production of calreticulin with a different amino acid sequence at one end. Somatic mutations in exon 9 of the gene CALR also associated with fibrosis.

The JAK2 gene, located on the short arm of chromosome 9 (9p24), encodes a protein that promotes the growth and proliferation of cells. Mutations in the JAK2 gene make a protein that appears to improve cell survival and increase blood cell production occur, so it is more likely the formation of blood clots. In addition, blood flows more slowly throughout the body, preventing the organs receive sufficient oxygen. The most common mutation (V617F or Val617Phe) replaces the amino acid valine for phenylalanine at amino acid position 617 in the protein. This mutation is found in about half of people with essential thrombocythemia. A small number of affected individuals have a somatic mutation in exon 12 of the JAK2 gene.

The MPL gene, located on the short arm of chromosome 1 (1p34), encoding the protein thrombopoietin receptor, which promotes the growth and proliferation of cells. This receptor is particularly important for proliferation of megakaryocytes, involved in blood clotting. Mutations in the gene cause MPL substitution of amino acid serine by asparagine at amino acid position 505 in the protein (or Ser505Asn S505N). The amino acid changes in position 505 or 515 leading to overproduction of abnormal megakaryocytes and increased platelet count. Excess platelets can cause thrombosis, leading to many signs and symptoms of essential thrombocythemia. Mutations in the gene MPL also cause congenital amegakaryocytic thrombocytopenia call (MVAC). This alteration begins in childhood and is characterized by a low number of megakaryocytes (megakaryocytopenia) and platelets (thrombocytopenia). MVAC can lead to impaired function of the bone marrow (bone marrow failure).

The TET2 gene, located on the long arm of chromosome 4 (4q24), encoding a protein whose function is unknown. Based on the role of similar proteins, researchers believe that TET2 protein involved in the regulation of the transcription, which is the first step in protein production. Somatic mutations in the gene are TET2 related polycythemia vera, a disorder characterized by uncontrolled production of erythrocytes. Other mutations TET2 gene are associated with certain types of cancers of blood cells (leukemia) and a disease of the blood and bone marrow called myelodysplastic syndrome.

The THPO gene, located on the long arm of chromosome 3 (3q27), encoding thrombopoietin protein that promotes the growth and proliferation of cells. This protein binds to thrombopoietin receptor activating and stimulating several signaling pathways that transmit chemical signals from outside the cell to the cell nucleus. These pathways are important in controlling the production of blood cells. Mutations in the gene THPO, cause overproduction of megakaryocytes and platelet count increased, which may cause thrombosis.

Most cases of essential thrombocytosis -trombocitemia essentially not inherited. This alteration is due to genetic mutations produced in the early stages of the formation of blood cells after conception. Less commonly, the alteration is inherited as an autosomal dominant, which means that a copy of the altered gene in each cell is sufficient to cause the disorder. When inherited, the condition is called essential thrombocytosis family.  

Tests in IVAMI: in IVAMI perform detection of mutations associated with essential thrombocytosis -trombocitemia essentially, by complete PCR amplification of the exons of CALR, JAK2, MPL, TET2 and THPO genes, respectively, and subsequent sequencing .

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).