What causes MPNs? 

Nobody really knows what causes myeloproliferative neoplasms (MPNs). There is no single factor known to trigger polycythaemia vera (PV) or essential thrombocythemia (ET) – they are most likely caused by a combination of different factors. Myelofibrosis (MF) is slightly different because it can develop on its own, or as a progression of PV or ET (known as secondary MF); between 10 and 15% MF cases develop from polycythemia vera or essential thrombocythemia.

What happens to cause blood cell abnormalities?

MPNs are often called ‘clonal blood stem cell disorders’, which means they result from a change (or mutation) in the DNA of a single blood stem cell. This change results in abnormal blood cell development and in the overproduction of blood cells.


Learn more about the bone marrow and stem cells »

In MPNs, the change in a single blood stem cell’s DNA, also known as the primary mutation, becomes more widespread when the affected stem cell divides (proliferates) and produces identical stem cells all with the same defect.


JAK Pathway

Many patients with MPNs have altered activity in the proteins that control signalling pathways, known as JAK proteins, which regulate blood cell production.

It’s this ‘dysregulated’ JAK pathway that results in many of the features of MPNs. The end result is that the body makes the wrong number of blood cells. It is the change in the number of blood cells and inflammatory chemicals (cytokines) that ultimately results in the symptoms commonly found in MPNs.

Studies suggest that a specific kind of mutation in the JAK2 protein is present in approximately 90-95% of patients with PV, and in around half those with ET and myelofibrosis (PMF).

It is important to note that even MPN patients without a JAK2 mutation have a ‘dysregulated’ JAK pathway. The ‘dysregulated’ JAK pathway may also be caused by different gene mutations, excess chemicals in the body (known as cytokines) as well as other unknown factors. Ultimately these may lead to the symptoms of ET, MF or PV.

Is it genetic?

Most people with a myeloproliferative neoplasm have no family history of the disease. In general, it is neither inherited nor passed on to your children. Further research is needed, however, to better understand genetic influences on what causes MPNs.

What has age got to do with it?

Mutations in dividing cells occur all the time and healthy cells have sophisticated mechanisms within them to stop these abnormalities. However the longer we live, the more chance we have of acquiring mutations that escape these safeguards. This is why MPNs are more common as we get older.