JAK2 is a molecule called an enzyme that exists in all people. Researchers made a dramatic discovery in 2005 when they found a mutation in the JAK2 molecule in people who have MPDs. Nearly all people with PV and about half those with ET and MF have the mutation. People are not born with it but develop it during their lives, most often in adulthood.

What is JAK2?

The answer to this question starts inside our bones. The long bones in our body contain a spongy tissue called bone marrow.

Inside the bone marrow are special “progenitor” cells or stem cells, which can grow into any of the three types of blood cells in our bodies: red blood cells, platelets, and white blood cells.

If we looked inside the stem cells, we would find different types of molecules. Some of these molecules form a communications pathway for messages traveling inside the cell. One of these molecules is an enzyme called JAK2.

JAK2’s role in cell production

When our bodies want to make more red blood cells for instance, a hormone called erythropoietin (EPO) is released into our bloodstream. The EPO hormone travels through the bloodstream and eventually reaches the bone marrow, where it finds the stem cells. The hormone then locks onto a receptor site on the surface of the stem cell, which then in turn locks onto the JAK2 molecule inside the cell. This changes the structure of the JAK2 molecule, so that the JAK2 can transmit the message forward to other proteins on the communications pathway. The message tells the cell nucleus to grow and produce more red blood cells.

What happens when JAK2 develops a mutation?

Many patients with MPDs develop a mutation in the JAK2 enzyme, and the mutation affects the way in which JAK2 operates. The JAK2 doesn’t simply transmit a signal in response to the EPO hormone but instead acts on its own, amplifying the signal from the receptor. The excessively strong signal causes the body to produce too many blood cells.

Does this discovery change things?

We now know that many patients carry the JAK2 mutation, while many do not. (About 50% of ET patients and about 97% of PV patients test positive for the JAK2 mutation). Professor Tony Green of Cambridge University amongst others has proposed that we may want to reclassify the way we look at MPDs. In the past, we saw the MPDs as three diseases, albeit with some overlaps – ET, PV and MF. The news on JAK2 may challenge this paradigm and completely alter the way we classify MPDs.

Are there two diseases?

Based on the new information, we might think of classifying the MPDs into two diseases: a JAK2 mutation-positive and a JAK2 mutation-negative disease. There is some strong evidence pointing to this view. For instance, patients who carry the JAK2 mutation share many disease attributes. Some of these patients produce more red blood cells, and some produce more platelets, but this may in fact be due to the patient’s particular genetic background or sex. Men, for example, produce more red blood cells. Perhaps we should look at JAK2 mutation-positive patients as having a single JAK2 positive MPD, rather than classifying them as ET or PV.

Chronic and accelerated phases

Each group of patients goes through a chronic phase, which can last for a long time. Some patients worsen and develop myelofibrosis (either a JAK2-positive or JAK2-negative version) – we can think of this as an “accelerated” phase of the disease. A very few patients may move into a “leukaemic” phase – in other words they develop leukaemia.The discovery of JAK2 is thus changing the way we think about these illnesses. What we’ve thought of for many years as three diseases – ET, PV, and MF – may instead be two diseases: JAK2 mutation-positive and JAK2 mutation-negative MPDs.

How can I be tested?

The JAK2 test is very simple, and it only requires a blood draw with a very small amount of blood. Results are available in one to two weeks. Results of the test will help your haematologist diagnose your disorder and potentially help him or her to optimise your treatment.