JAK2

JAK2 is involved in blood cell growth and development, and mutations are the cause of many different blood disorders.  

In addition to modulating blood cell growth, JAK2 is somewhat involved in the immune system and therefore has been studied in relation to Crohn’s Disease and colon and rectal cancer [R].  

Although not studied, this SNP is believed to play a part in illnesses caused by JAK2 protein mutations [R].

The JAK2 gene provides instructions for making a protein that promotes the growth and division (proliferation) of cells. This protein is part of a signaling pathway called the JAK/STAT pathway, which transmits chemical signals from outside the cell to the cell’s nucleus. The JAK2 protein is especially important for controlling the production of blood cells from hematopoietic stem cells. These stem cells are located within the bone marrow and have the potential to develop into red blood cells, white blood cells, and platelets.

The JAK2 gene is a part of the Janus Kinase family, which are involved in acquired autoimmune disorders and Crohn’s disease R

The JAK2 gene is associated with the prolactin receptor  R

JAK2 is activated during Prolactin receptor binding; this activation makes JAK2 an indicator protein for prolactin binding R Prolactin is a hormone that produces milk during breastfeeding R

The JAK2 gene provides instructions for cell growth and division of red blood cells

A variation of the JAK2 gene, known as the JAK2V617F mutation, causes the body to constantly produce red blood cells, white blood cells, and blood platelets R

JAK2 gene is mainly produced in bone marrow, where it acts like an On-Off switch, signaling when the body should start/stop producing RBCs, WBCs, and platelets R

The JAK2V617F mutation turns that On-Off switch to always On  

This group of blood diseases is referred to as Myeloproliferative Neoplasms R

The JAK2 gene also influences immune cells that are directly associated with Crohn’s disease R

Crohn’s disease is categorized by chronic inflammation of the gut, possibly due to irregular immune response to bacteria in the gut R

White blood cells mistake normal gut bacteria, that aids in digestion, as dangerous and removes it, causing the gut to not properly digest food R

     essential thrombocythemia Some gene mutations are acquired during a person’s lifetime and are present only in certain cells. These changes, which are called somatic mutations, are not inherited. Somatic mutations in the JAK2 gene are associated with essential thrombocythemia, a disorder characterized by an increased number of platelets, the blood cells involved in normal blood clotting. The most common mutation (written as Val617Phe or V617F) replaces the protein building block (amino acid) valine with the amino acid phenylalanine at position 617 in the protein. This particular mutation is found in approximately half of people with essential thrombocythemia. A small number of affected individuals have a somatic mutation in another part of the JAK2 gene known as exon 12. The V617F JAK2 gene mutation results in the production of a JAK2 protein that is constantly turned on (constitutively activated), which, in essential thrombocythemia, leads to the overproduction of abnormal blood cells called megakaryocytes. Because platelets are formed from megakaryocytes, the overproduction of megakaryocytes results in an increased number of platelets. Excess platelets can cause abnormal blood clotting (thrombosis), which leads to many signs and symptoms of essential thrombocythemia. polycythemia vera Somatic mutations in the JAK2 gene are associated with polycythemia vera, a disorder characterized by uncontrolled blood cell production. The V617F mutation is found in approximately 96 percent of people with polycythemia vera. About 3 percent of affected individuals have a somatic mutation in the exon 12 region of the JAK2 gene. JAK2 gene mutations result in the production of a constitutively activated JAK2 protein, which seems to improve the survival of the cell and increase production of blood cells. With so many extra cells in the bloodstream, abnormal blood clots are more likely to form. In addition, the thicker blood flows more slowly throughout the body, which prevents organs from receiving enough oxygen. Many of the signs and symptoms of polycythemia vera are related to a lack of oxygen in body tissues. primary myelofibrosis Somatic JAK2 gene mutations are also associated with primary myelofibrosis, a condition in which bone marrow is replaced by scar tissue (fibrosis). The V617F mutation is found in approximately half of individuals with primary myelofibrosis. A small number of people with this condition have mutations in the exon 12 region of the gene. These JAK2 gene mutations result in a constitutively active JAK2 protein, which leads to the overproduction of abnormal megakaryocytes. These megakaryocytes stimulate other cells to release collagen, a protein that normally provides structural support for the cells in the bone marrow but causes scar tissue formation in primary myelofibrosis. Because of the fibrosis, the bone marrow cannot produce enough normal blood cells, leading to the signs and symptoms of the condition. other disorders Somatic JAK2 gene mutations are also associated with several related conditions. The V617F mutation is occasionally found in people with cancer of blood-forming cells (leukemia) or other bone marrow disorders. Budd-Chiari syndrome, which results from a blocked vein in the liver, can also be associated with the V617F mutation when it is caused by an underlying bone marrow disorder. It is unknown how one particular mutation can be associated with several conditions.

     The JAK2 gene provides instructions for making a protein that promotes the growth and division (proliferation) of cells. This protein is part of a signaling pathway called the JAK/STAT pathway, which transmits chemical signals from outside the cell to the cell’s nucleus. The JAK2 protein is especially important for controlling the production of blood cells from hematopoietic stem cells. These stem cells are located within the bone marrow and have the potential to develop into red blood cells, white blood cells, and platelets.

Fix/Read: Natural STAT3 Inhibitors– What will inhibit STAT3, will also inhibit JAK2.They are part of the same pathway.