فارسی
Janus kinase 2 (commonly called JAK2) is a non-receptor tyrosine kinase. The JAK2 gene provides instructions for making a protein that causes cells to grow and divide (multiply). This protein is part of a signaling pathway called the JAK/STAT pathway, which transmits chemical signals from the outside of the cell to the cell nucleus. The JAK2 protein promotes cell growth and division and is particularly important for controlling the production of blood cells from hematopoietic stem cells in the bone marrow. These stem cells are located inside the bone marrow and have the potential to become red blood cells, white blood cells, and platelets. Mutations in JAK2 have been identified in ALL and other hematologic malignancies. Bone marrow disorders caused by JAK2 mutations manifest as myeloproliferative neoplasms (MPNs), in which the bone marrow produces low numbers of white blood cells, red blood cells, or platelets. Some of the MPNs most commonly associated with JAK2 mutations include:
– Polycythemia vera (PV) – bone marrow produces too many red blood cells
– Essential thrombocythemia (ET) – there are many platelet-producing cells (megakaryocytes) in the bone marrow.
– Primary myelofibrosis (PMF), also known as chronic idiopathic myelofibrosis or agnogenic myeloid metaplasia – There are many cells and platelet-producing cells that produce scar tissue in the bone marrow.
In general, JAK2 has the highest prevalence of changes in 2.65% of all cancers with lung adenocarcinoma, myeloproliferative neoplasm, invasive ductal carcinoma of the breast, polycythemia vera and colon adenocarcinoma. The most common changes in JAK2 are: JAK2 mutation (2.05%), JAK2 exon 14 mutation (0.94%), JAK2 V617F (1.11%), JAK2 loss (0.30%) and JAK2 gain (0.29%).
The primary test to check for JAK2 mutations is JAK2 V617F, which is named for a mutation at a specific location in the JAK2 gene. The JAK2 V617F mutation, unlike inherited mutations, is acquired and results in a DNA nucleotide base pair change. In JAK2, this type of mutation, called a point mutation, replaces the naturally occurring amino acid valine with phenylalanine. This amino acid change results in the JAK2 protein being constantly “on” and leading to uncontrolled blood cell production. Other mutations in the JAK2 gene are also associated with MPNs. More than 50 different mutations have been identified. There are tests to detect mutations in JAK2 exon 12 and other mutations other than V617F.
The sampling method is that the blood sample is taken by inserting a needle into the arm vein. Sometimes a bone marrow aspiration and biopsy may be done to collect a sample for testing. The JAK2 V617F mutation characterizes most MPNs lacking the Philadelphia chromosome and rarely occurs in de novo acute myeloid leukemia (AML-DN). Indeed, this mutation is often detected in AML following a previous MPN diagnosis, although, it is notable that some JAK2-positive MPNs progress to JAK2-negative AML. As mentioned, myeloproliferative neoplasms (MPNs) comprise a group of clonal stem cell disorders associated with a high prevalence of mutations in JAK2, overproduction of mature blood elements, and variable rates of transformation to AML. Transformation to AML occurs in 2–5% of patients with essential thrombocythemia (ET) or polycythemia vera (PV)3,4 and 15–30% of patients with primary myelofibrosis (PMF), as well as in untreated patients. occur, suggesting that leukemic transformation is part of the natural history of these disorders. Of note, recent studies have shown a role for the JAK2 V617F mutation in promoting the generation of clones with more genetic damage, suggesting that disease progression may be partially driven by mutant JAK2 expression.
refrences:
