The JAK2 enzyme has long been associated with myelofibrosis (MF). The newest and most promising treatments stop or slow down the enzyme, which may help slow down the disease.

Scientist preparing sample for analysis
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To better understand the JAK2 gene and enzyme, it’s helpful to have a basic understanding of how genes and enzymes work together in our bodies.

Our genes are the instructions or blueprints for our bodies to function. We have a set of these instructions inside every cell of our body. They tell our cells how to make proteins, which go on to make enzymes.

The enzymes and proteins relay messages to other parts of the body to perform certain tasks, such as helping with digestion, promoting cell growth, or protecting our body from infections.

As our cells grow and divide, our genes within the cells can get mutations. The cell passes that mutation on to every cell it creates. When a gene gets a mutation, it can make the blueprints difficult to read.

Sometimes, the mutation creates a mistake so unreadable that the cell can’t create any protein. Other times, the mutation causes the protein to work overtime or to stay constantly turned on. When a mutation disrupts the protein and enzyme function, it can cause disease in the body.

The JAK2 gene gives our cells instructions for making the JAK2 protein, which encourages the growth of cells. The JAK2 gene and enzyme are very important for controlling the growth and production of cells.

They’re especially important for the growth and production of blood cells. The JAK2 enzyme is hard at work in the stem cells in our bone marrow. Also known as hematopoietic stem cells, these cells are responsible for creating new blood cells.

The JAK2 also plays a role in modulating the body’s immune response.

Mutations found in people with MF cause the JAK2 enzyme to always stay turned on. This means that the JAK2 enzyme is constantly working, which leads to overproduction of cells called megakaryocytes.

These megakaryocytes tell other cells to release collagen. As a result, scar tissue starts to build up in the bone marrow — the telltale sign of MF.

Mutations in JAK2 are also linked to other blood disorders. Most frequently, the mutations are linked to a condition called polycythemia vera (PV). In PV, the JAK2 mutation causes uncontrolled blood cell production.

Around 10–15% of people with PV will go on to develop MF. Researchers don’t know what causes some people with JAK2 mutations to develop MF while others develop PV instead.

The JAK2 mutation can also cause essential thrombocytosis (or thrombocythemia), another myeloproliferative disorder like PV. Around half of patients with this disorder have the JAK2 mutation.

JAK2 mutations are also linked to immune dysregulation.

Because JAK2 mutations have been found in more than half of people with MF and over 90% of people with PV, it has been the subject of many research projects.

JAK inhibitors are drugs that slow down the activity of JAK2. When the enzyme activity is slowed down, the enzyme isn’t always turned on. This leads to less megakaryocyte and collagen production, ultimately slowing the scar tissue buildup in MF.

Food and Drug Administration (FDA)-approved JAK2 inhibitors include:

  • ruxolitinib (Jakafi)
  • fedratinib (Inrebic)
  • pacritinib (Vonjo)

The drug ruxolitinib also regulates the production of blood cells. It does this by slowing the function of JAK2 in hematopoietic stem cells. This makes it helpful in both PV and MF.

Researchers are also working on how to manipulate this gene and enzyme to hopefully find a better treatment or a cure for MF.

Other JAK inhibitors are used for conditions such as rheumatoid arthritis and psoriasis, including baricitinib (Olumiant), tofacitinib (Xeljanz), and upadacitinib (Rinvoq).