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What are Myeloproliferative Neoplasms (MPNs)?

‘Myelo’ is the Greek word for marrow and ‘proliferative’ is another word for growing or reproducing. Myeloproliferative neoplasms are a group of disorders in which the bone marrow cells grow and reproduce abnormally. In the myeloproliferative neoplasms, abnormal bone marrow stem cells produce excess numbers of one or more types of blood cells (red cells, white cells and/or platelets). These abnormal cells change the thickness of the blood, and sometimes have abnormal function. MPNs can cause serious health problems unless properly treated and controlled.

MPNs are chronic diseases that, in most cases, remain stable for many years and progress gradually over time.

MPNs are sometimes described as being clonal blood stem cell disorders. This means that they result from a change, or mutation, in the DNA of a single blood stem cell. This change (or changes) results in abnormal blood cell development and in this case the overproduction of blood cells.

In MPNs the original mutation is preserved when the affected stem cell divides (proliferates) and produces a ‘clone’: a group of identical stem cells all with the same defect. Mutations in dividing cells occur all the time and healthy cells have sophisticated mechanisms within them to stop these abnormalities persisting. But the longer we live, the more chance we have of acquiring mutations that manage to escape these safeguards.

MPNs are usually described according to the type of blood cell which is most affected. MPNs are closely related diseases, so it’s not uncommon for people to have features of more than one MPN when they are first diagnosed, or during the course of their illness. In some cases, one disorder may transform over time to another, or to a type of leukaemia called acute myeloid leukaemia.

Who gets MPN?

Most people with an MPN have no family history of the disease. MPNs are more commonly diagnosed in people over the age of 50 although an MPN can rarely occur in younger people, even very rarely in children.

What causes MPN?

The exact cause of MPNs remains unknown but there are likely to be a number of factors involved. That’s why MPNs, like most leukaemias and other cancers, become more common as we get older. A mutation of a particular gene (a segment of DNA that makes proteins) known as Janus kinase 2 (JAK2) is found in a large proportion of people with MPNs. The exact meaning of this mutation remains unclear but it appears to play a role in the overproduction of blood cells seen in these disorders. The discovery of a mutation in the JAK2 gene is important because it is likely to have a significant impact on the way MPNs are diagnosed and treated.

Long-term exposure to high levels of benzene or very high doses of ionising radiation may increase the risk of myelofibrosis in a small number of cases. Around one third of people with myelofibrosis have been previously diagnosed with polycythaemia or essential thrombocythaemia.

What are the different types of MPN?

Myeloproliferative neoplasms are usually described according to the type of blood cell which is most affected. There are three main types of myeloproliferative neoplasms –

  • Polycythaemia vera (PV) – too many red cells
  • Essential thrombocythaemia (ET) – too many platelets
  • Myelofibrosis (MF) – bone marrow tissue is replaced by fibrous scar-like tissue

PV, ET and MF are closely related diseases, so it is not uncommon for people to have features of more than one of these diseases when they are first diagnosed, or during the course of their illness. In some cases, one of these diseases may transform over time to another. All myeloproliferative neoplasms can transform into a type of leukaemia called acute myeloid leukaemia (AML).

Less common types of myeloproliferative neoplasms include:

  • Chronic neutrophilic leukaemia (CNL) – too many neutrophils (a type of white cell) in blood and bone marrow
  • Chronic eosinophilic leukaemia (CEL) / hypereosinophilic syndrome – too many eosinophils (another type of white cell) in blood and bone marrow
  • Chronic myelomonocytic leukaemia (CMML) – too many monocytes (a type of white cell).
  • Myeloproliferative neoplasm– unclassifiable

How common is MPN?

Myeloproliferative neoplasms are a rare group of diseases. Polycythaemia vera is diagnosed in an estimated 250 Australians each year, essential thrombocythaemia around 200 and myelofibrosis an estimated 150. The rarer sub types of MPN, as a group, are diagnosed in less than 50 Australians per year.

Polycythaemia (rubra) vera – (PV)

Polycythaemia (rubra) vera (PV) is a disorder in which too many red cells are produced in the bone marrow. These cells accumulate in the bone marrow and in the blood stream where they increase the blood volume and cause the blood to become thicker, or more ‘viscous’ than normal. In many people with PV, too many platelets and white cells can also be produced. PV is a rare chronic disease diagnosed in an estimated 250 people in Australia each year. Although it can occur at any age, PV usually affects older people, with most patients diagnosed over the age of 50. PV is rare in children and young adults. It occurs more commonly in males than in females. Secondary or reactive polycythaemia In secondary or reactive polycythaemia, red cell production is increased in response to excess amounts of erythropoietin (a red cell growth factor) circulating in the bloodstream. Erythropoietin is a useful compensatory mechanism that helps the body to produce more red cells and haemoglobin to transport more oxygen around the body. In a condition known as relative, apparent or spurious polycythaemia, the volume of plasma (the liquid portion of the blood) is reduced, usually as a result of dehydration, vomiting or diuretic (fluid loss) therapy. This increases the concentration of red cells in the blood but the actual total number of red cells remains normal

Essential thrombocythaemia – (ET)

Essential thrombocythaemia (ET) is a disorder in which too many platelets are produced in the bone marrow. Platelets are normally needed in the body to control bleeding. However, excess numbers of platelets can lead to abnormal blood clotting, which can block the flow of blood in the blood vessels. There are a number of conditions that can cause a rise in the number of platelets in the circulating blood (thrombocytosis). These include bleeding, infection and some types of cancer. In ET, however, the blood platelet count is persistently elevated as a result of increased bone marrow production of platelets, in the absence of any identifiable cause. Like polycythaemia vera, ET is a rare chronic disease diagnosed in an estimated 200 people in Australia each year. Although it can occur at any age, even (rarely) in children, ET usually affects older people, with most patients diagnosed between the ages of 50 and 70. It occurs more frequently in females than males.

Primary myelofibrosis – (PMF or MF)

Primary myelofibrosis is a disorder in which normal bone marrow tissue is gradually replaced with a fibrous scar-like material. Over time, this leads to progressive bone marrow failure. Under normal conditions, the bone marrow provides a fine network of fibres on which the stem cells can divide and grow. Specialised cells in the bone marrow known as fibroblasts make these fibres. In myelofibrosis, chemicals released by high numbers of platelets and abnormal megakaryocytes (platelet forming cells) over-stimulate the fibroblasts. This results in the overgrowth of thick coarse fibres in the bone marrow, which gradually replace normal bone marrow tissue. Over time, this destroys the normal bone marrow environment, preventing the production of adequate numbers of red cells, white cells and platelets. This results in anaemia, low platelet counts and the production of blood cells in areas outside the bone marrow for example in the spleen and liver, which become enlarged as a result. Myelofibrosis is a rare chronic disorder diagnosed in an estimated 150 people in Australia each year. It can occur at any age but is usually diagnosed later in life, between the ages of 60 and 70 years. The cause of myelofibrosis remains largely unknown. It can be subclassified depending upon the presence or absence of the JAK2, MPL or CALR gene mutations that are associated with the MPNs. Long-term exposure to high levels of benzene or very high doses of ionising radiation may increase the risk of primary myelofibrosis in a small number of cases. Around one third of people with myelofibrosis have been previously diagnosed with polycythaemia (post-polycythaemic myelofibrosis) or essential thrombocythaemia (post-thrombocythaemic myelofibrosis).

Myeloproliferative Neoplasm – Unclassifiable (MPN-U)

The 2016 World Health Organization (WHO) classification system for tumours of the hematopoietic and lymphoid tissues was published in September 2017. MPN-Unclassifiable (MPN-U) remains one of the seven subcategories of myeloproliferative neoplasms (MPN) covering cases with features of one or more myeloproliferative neoplasms but which do not fulfil the diagnostic criteria for one of the 3 classic MPNs (ET, PV, or MF), chronic myeloid leukaemia (CML), chronic neutrophilic leukaemia (CNL) or chronic eosinophilic leukaemia – not otherwise specified (CEL-NOS).

The combination of clinical, morphological (blood count and bone marrow findings), and molecular genetic features is used to define each MPN subcategory. The WHO MPN sub-category of MPN-U includes MPN-like neoplasms that cannot be clearly classified as one of the other subcategories of MPNs. Patients with MPN-U might present with otherwise unexplained thrombosis, especially splanchnic vein thrombosis, which is associated with normal blood count.

The reported incidence of MPN-U varies significantly in different studies with most studies showing an incidence of 10–15%. When the 2016 WHO criteria have been applied the incidence is reduced to <5%. Patients with MPN-U are treated based on their clinical abnormalities, blood count and bone marrow findings and molecular abnormalities. In some cases, a diagnosis of MPN- U may reflect a very early stage of the disease, and sub- classification may be possible as the disease progresses.

Further Information:

For more information, please see the Leukaemia Foundation booklet – Myeloproliferative Neoplasms (MPN) – A Guide for Patients and families

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