What are MPNs?

Myeloproliferative Neoplasms (MPNs) is the name given to a group of conditions sometimes referred to as blood cancers.

MPNs originate in the bone marrow – the soft tissue in the middle of the bones where blood cells are made. In a healthy person, bone marrow makes blood stem cells that, in time, develop into mature blood cells – red blood cells, white blood cells or platelets.

Each of these “mature” blood cells is vital to maintaining our health. Red blood cells carry oxygen and other materials to the tissues of your body; white blood cells fight infection and disease; platelets help to prevent bleeding by causing blood clots to form.

MPNs are stem cell disorders and develop when abnormal stem cells produce excess quantities of one or more of these blood cell types. As these blood cells are unable to function properly, they can trigger serious health problems if not treated and controlled.

MPNs are virtually unknown in children, and very rare in young adults. All three conditions primarily affect people over the age of 50.

It’s useful to remember that MPNs are chronic diseases – in most cases they remain stable for many years or may progress gradually over time. Many people with MPNs live normal lives for years without experiencing complications.

The different types of chronic MPNs

There are four main types of chronic MPN, the key difference being the type of blood cell being most over-produced in each condition.

Essential thrombocythemia (ET) ET (also previously known as primary thrombocythemia) occurs when the bone marrow makes more platelets than the body needs. Platelets are needed to help the blood clot, but because there are too many of them, in people with ET they don’t work properly. This results in serious complications like thrombosis – where excess platelets cause a blood clot that blocks a vein or artery and stops blood flowing – and excess bleeding.

Myelofibrosis (MF) MF is a disorder of the bone marrow. It occurs when abnormal stem cells in the bone marrow produce too many mature cells causing chronic inflammation and development of scar tissue (fibrosis). This scarring means the marrow is not able to make enough blood cells. The liver and spleen then compensate by producing their own blood cells, causing them to swell in size, which may lead to liver failure. MF can also cause anaemia and bleeding problems, as well as leaving patients at higher risk of infections.

Polycythemia vera (PV) In PV, too many red blood cells are produced (white blood cells and platelet counts are also increased). An increase in red blood cells makes blood thicker than normal, meaning clots form more easily. Around 30 per cent of people with PV experience blood clots. These can, in turn, cause blockages in arteries and veins, leading to complications such as heart attacks or strokes. Because thicker blood doesn’t flow as quickly through your body as normal blood, the body’s organs suffer from lack of oxygen. This in turn causes other serious problems such as angina and heart failure.

Chronic myeloid leukemia (CML) is also an MPN. CML is a chronic, progressive hematologic disorder in which there is abnormal production of blood cells by stem cells in the bone marrow. Most people with CML have a genetic mutation in which part of the genetic material from one chromosome is transferred to another chromosome. The resulting chromosome is called the Philadelphia chromosome. This chromosomal abnormality results in a great overproduction of white blood cells by the bone marrow.

Less common types of MPNs include:

  • Chronic neutrophilic leukemia (CNL)
  • Chronic eosinophilic leukemia (CEL) / hypereosinophilic syndrome
  • Chronic myelomonocytic leukemia (CMML)
  • Systemic mastocytosis

ET, MF and PV are all closely related diseases, and people affected may experience similar symptoms such as anemia and itching. A common symptom among all MPNs is an enlarged spleen (splenomegaly), which affects up to 75% of patients with PV. This occurs when the spleen compensates for bone marrow not working properly by producing red blood cells (known as extra medullary erythropeiesis), causing it to enlarge. In some cases, the liver may also become enlarged (known as hepatomegaly).

What causes MPNs?

It is not clear what causes MPNs. There is no single factor known to trigger PV or ET – they are most likely caused by a number of different factors. MF is slightly different because it can develop on its own (idiopathic) or, in some cases, develop in people who have ET or PV (known as secondary MF).

Role of stem cells: MPNs are often called “monoclonal blood stem cell disorders,” which means they result from a change (or mutation) in the DNA of a single blood cell. This change results in abnormal blood cell development and the overproduction of blood 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 and produces clones of identical stem cells, all with the same defect.

Gene mutations: A number of gene mutations have been identified in people with MPNs, including mutations in the JAK2, MPL and CALR genes. About 50% to 60% of patients with MF will have the JAK2 gene mutation, 24% will have the CALR gene mutation and 5% to 10% will have the MPL gene mutation. Around 95% of people with PV have a JAK2 mutation. Around 60% of people with ET have the JAK2 gene mutation, 30% have the CALR mutation and 5% have the MPL mutation.

Lack of oxygen: Another type of polycythaemia, called secondary polycythaemia, isn’t related to the altered JAK2 gene, but is caused by long-term exposure to low oxygen levels. If your body doesn’t have access to enough oxygen, it produces more of a hormone called erythropoietin (EPO), which in turn can lead to the production of more red blood cells than normal. This results in thicker blood, and PV. Therefore, people who have severe heart or lung disease are at risk of developing secondary polycythaemia, as are people who smoke, spend long hours at high altitude or who are exposed to high levels of carbon monoxide.

Other known risk factors for MPNs

A number of factors may increase the chances of developing an MPN.

  • Chemicals and radiation. Exposure to certain chemicals and to radiation may both increase risk, but it is extremely rare that levels of either are high enough to cause illness.
  • Autoimmune disease. One study found that a history of any autoimmune disease was associated with a ‘modest but statistically significant’ increased risk of MPNs.
  • Family history. While MPNs are not believed to be hereditary, a study has found that first-degree relatives of people with MPNs had a significantly increased risk of MPNs, suggesting that close family members are more likely to have genes that predispose them to MPNs. Clusters of families with MPNs have also been reported, suggesting it can run in families in some people.
  • Age. MPNs largely affect people over the age of 50. Mutations in dividing cells occur all the time, and healthy cells have sophisticated mechanisms to stop these abnormalities. However, the longer we live, the more chance we have of acquiring mutations that can bypass these safeguards. That’s why MPNs are more common in people over 50.
  • Gender. ET affects twice as many women as men. PV affects slightly more men than women, while MF affects men and women in roughly equal numbers.
  • Race. Studies show that MF is more commonly found in white people than among people of other races. There is also an increased prevalence among Ashkenazi Jews.

Are MPNs common?

Most people diagnosed with MPNs have never heard of the condition before. It is virtually unknown in children, and very rare in young adults (particularly MF and PV). All three conditions primarily affect people over the age of 50.

Essential thrombocythaemia (ET): ET prevalence in the US in 2010 ranged from 39-57 cases per 100,000 population.It is most common among those over the age of 60, although 20% of people with ET are under the age of 40. The average age at diagnosis is between 65 and 70 years. It’s more common among women, with two women diagnosed for every one man.

Myelofibrosis (MF): In the US in 2010, MF prevalence ranged from 3.6 to 5.7 per 100,000.It can be diagnosed at any age, but is most common in people aged between 60 and 70 and affects men and women in relatively equal numbers. Around one third of people who are diagnosed with MF will have previously been diagnosed with ET or PV. This is known as post-polycythemia vera MF (post-PV MF) or post-essential thrombocythemia MF (post-ET MF).

Polycythemia vera (PV): In 2010 PV prevalence estimates in the US ranged from 45 to 57 cases per 100,000. It is very rare in children and young adults, mostly affects people over the age of 50, and is more common in men than women.

Diagnosing an MPN

Diagnosing an MPN can be challenging. In the early stages, there are often no symptoms, and even when symptoms appear, such as fatigue, they can often be mistaken for signs of other diseases. It is not unusual for an MPN to be detected during tests for unrelated problems. Doctors use a combination of lab tests, examining the blood and bone marrow, and physical tests, to diagnose MPNs. Typical tests may include

Physical examination. Your body is checked for anything that seems unusual. A doctor will also compile a history of your health, any relevant lifestyle information and any past illnesses and treatments.

Complete/full blood count. A sample of blood is taken and checked for:

  • The number of red blood cells and platelets
  • he number of white blood cells
  • The amount of hemoglobin (the protein that carries oxygen) in the red blood cells
  • he portion of the blood sample made up of red blood cells

Peripheral blood smear. A sample of blood is checked for:

  • Red blood cells shaped like teardrops
  • The number and kinds of white blood cells.
  • The number of platelets
  • The presence of blast cells

Bone marrow aspiration and biopsy. Bone marrow, blood and a small piece of bone will be removed by inserting a hollow needle into the hipbone or breastbone. This is then checked for abnormal cells.

Cytogenetic analysis. Cells from a sample of blood or bone marrow are viewed under a microscope to look for certain changes in the chromosomes, which can diagnose or rule out certain diseases or disorders.

Gene mutation test. Bone marrow or blood samples are checked in a lab for mutations in genes. A JAK2 gene mutation is often found in patients with polycythemia vera, essential thrombocythemia, or primary myelofibrosis. MPL or CALR gene mutations are found in patients with essential thrombocythemia or primary myelofibrosis.

Learn about individual MPNs:

The effects MPNs can have on different parts of the body


Brain

Thicker blood and/or higher numbers of platelets can cause blood clots in the arteries that interfere with the blood and oxygen supply to the brain. This can result in a stroke.

Heart

In PV, a lack of oxygen-rich blood reaching the heart may result in heart failure or angina (chest pain).

Liver

In MF and PV, the body uses organs other than the bone marrow to make blood cells. This can cause the liver to become enlarged (hepatomegaly).

Spleen

MF and PV affect the bone marrow, and its ability to make red blood cells. This means the spleen may take over the job, causing it to enlarge (called splenomegaly). An enlarged spleen may put pressure on the stomach, causing a feeling of fullness, indigestion and loss of appetite, which in turn can lead to weight loss.

Blood

In PV, the extra blood cells make the blood thicker and move more slowly, which can lead to clots as well as excess bleeding and bruising. In ET, excess platelets are produced, which may also lead to blood clots. These blood clots may affect the blood and oxygen supply to the heart (which may lead to heart attacks), the brain (which may trigger a stroke), lungs, kidneys and liver. In MF, the changes in blood cells tends to result in a lack of the oxygen-rich red blood cells, which may cause anaemia, leaving people affected feeling tired, weak and short of breath.

Skin

A higher than normal level of red blood cells may cause a red complexion, as well as reddening of the palms, soles of feet, ear lobes, mucous membranes and eyes. Excessive sweating, especially at night (known as night sweats) and itching (also known as pruritis) can also be caused by MPNs, usually as a result of chronic inflammation.

Hands and feet

PV and ET can both cause an intense burning pain, and increased skin temperature in the feet (and sometimes the hands). This is known as erythromelalgia.

Bones

The hardening of the bone marrow and inflammation of the connective tissue around the bones may lead to severe bone and/or joint pain.

Joints

In MF, extra blood cells can lead to a build-up of uric acid, resulting in painful swelling in a joint (gouty arthritis), usually the big toe.