Polycythemia vera (polycythemia vera) - Genes JAK2 and TET2

Polycythemia vera is a process characterized by an increase in the number of erythrocytes in the bloodstream. Affected individuals may also have an excess of white blood cells and platelets. These extra cells cause blood is thicker than normal. As a result, individuals with polycythemia vera have an increased risk of deep vein thrombosis. If a thrombus dislodges the bloodstream and reaches the lungs, it may cause pulmonary embolism. Affected individuals also have a higher risk of coronary events and stroke caused by blood clots in the heart and brain, respectively.

Polycythemia vera usually develops in adulthood, around age 60, although it rarely occurs in children and young adults. This process does not cause any symptoms in its early stages. Some people with polycythemia vera have headache, dizziness, tinnitus (tinnitus), impaired vision, or itchy skin. Other complications of polycythemia vera include splenomegaly, stomach ulcers, gout, heart disease and leukemia.

This process is due to mutations in JAK2 and TET2 genes. Although it is unclear exactly how polycythemia vera starts, it is believed to begin when mutations in the DNA of a hematopoietic stem cell occur. These stem cells are found in bone marrow and have the potential to erythrocytes, leukocytes and platelets. JAK2 gene mutations appear to be particularly responsible for the development of polycythemia vera, because nearly all affected individuals have a mutation in this gene.

The JAK2 gene, located on the short arm of chromosome 9 (9p24), encodes a protein that promotes the growth and cell proliferation. This protein is part of the signaling pathway JAK / STAT, which transmits chemical signals from outside the cell to the cell nucleus. The JAK2 protein is particularly important to control the production of blood cells from hematopoietic stem cells. Somatic mutations in the JAK2 gene are associated with polycythemia vera. Of these, the V617F mutation is found in approximately 96% of those affected. Approximately 3% of those affected have a somatic mutation in the region of exon 12 of the JAK2 gene. Mutations of the JAK2 gene coding result in a constitutively active JAK2 protein, which appears to improve cell survival and increase the production of blood cells. Because of this, there is an increased risk of formation of abnormal blood clots. In addition, the denser blood flows more slowly through the body, which prevents the organs receive sufficient oxygen. Many of the signs and symptoms of polycythemia vera are related to the lack of oxygen in body tissues.

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, it is believed that TET2 protein is involved in regulating the transcription process. Although this protein is found throughout the body, it can play a particularly important role in the production of blood cells from hematopoietic stem cells. Furthermore, TET2 protein appears to act as a tumor suppressor. Although mutations in the TET2 gene found in about 16% of people with polycythemia vera, it is unclear what role these mutations in disease development.

Most cases are hereditary polycythemia vera. This process is associated with somatic genetic changes, which means that are acquired during the life of a person and are present only in certain cells. In rare cases, polycythemia vera has been found in families. In some of these families, the risk of developing polycythemia vera appears to have an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means that a copy of an altered gene in each cell is sufficient to increase the risk of developing polycythemia vera. In these families, individuals seem to inherit an increased risk of polycythemia vera, not the disease itself.

Tests performed in IVAMI: in IVAMI perform detection of mutations associated with polycythemia vera, by complete PCR amplification of the exons of JAK2 and TET2 genes, respectively, and subsequent sequencing. It is recommended to begin the study by exon 12 and 14 of the JAK2 gene, where most of the genetic anomalies are localized, with possible reduction of time and cost involved in most cases. If negative result is the possibility of completing the study by amplifying and sequencing the other exons and TET2 JAK2 gene.

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).