Myeloproliferative neoplasms

Last Review Date: January 13, 2020

What are they?

Myeloproliferative neoplasms (MPNs) are a subset of bone marrow disorders. They are a group of four diseases characterised by an overproduction of one or more types of blood or fibre cells in the bone marrow. Bone marrow is a soft fatty tissue that is located in the centre of the body's larger bones. It contains a fibrous network, a population of undifferentiated pluripotent stem cells, and a mixture of red blood cells (RBC), white blood cells (WBC), and platelets in various stages of maturity.

Normally, the body maintains a dynamic but relatively stable number of blood cells in circulation. As cells age, die, or are removed from circulation, new ones are made in the marrow to replace them. When a particular kind of blood cell is needed, some of the stem cells in the bone marrow begin to change, becoming the immature ‘blast’ forms of whatever cell type is in short supply. These blasts mature to become white blood cells, red blood cells or platelets. Usually only fully mature cells are released into circulation.

With an MPN, excessive production of a cell’s precursor leads to an increased number of that type of mature cell and to a corresponding increase or decrease in the number of other blood cells, which may be inhibited and crowded out. This results in symptoms related to blood cell overproduction, shortages and dysfunction throughout the body.

The actual genetic event that leads to the development of several MPNs has been studied. Doctors can use the measurement of these abnormal genes or the proteins they produce to diagnose and measure the effectiveness of treatment. These measurements are done by very specialized molecular techniques and generally only available from specialised laboratories. Your doctor may have to send your blood or bone marrow sample away to a special laboratory for the results.

The diseases included in the group of MPN are:

  • Chronic myelogenous (myeloid) leukaemia (CML), a disease that leads to an overproduction of myelocytes, precursor to granulocytes - white blood cells that digest and kill invading microorganisms. Often, these overproduced cells do not function normally. CML is rare in children. It is an acquired condition that begins in an immature stem cell in the bone marrow when pieces from two chromosomes (9 and 22) break off and switch places (translocation). This results in an altered, fused gene (BCR/ABL) on chromosome 22, the ABL gene from chromosome 9 and the BCR gene from chromosome 21.  The abnormal chromosome is labelled t(9;21)(q34;q11) which describes the chromosomes from which is arises (9 and 21) and the part of the chromosome where the break and translocation occurs (q34 and q11).  It is also known as the Philadelphia chromosome. The BCR-ABL fusion gene produces copies of the BCR-ABL gene and proteins with abnormal tyrosine kinase activity that affect cell growth and regulation. This leads to an overproduction of granulocytic white blood cells, many with the BCR/ABL translocation, and the presence of both mature and immature cells in the bloodstream. Diagnosis is suspected when a pathologist looks at a patient’s peripheral blood which has a characteristic mix of mature and immature granulocytes. The diagnosis is confirmed by identifying and measuring the Philadelphia chromosome or the BCR/ABL gene in the blood or bone marrow and examining the bone marrow. Treatment is now available with a specialised small molecule drugs called tyrosine kinase inhibitor which bind specifically to the BCR-ABL tyrosine kinase and stop it working. Imatinib (also known by its trade name as Glivec®) is the drug that most patients are started on when they are diagnosed with CML. Measurements of the BCR/ABL gene with a blood test are used to monitor the effectiveness of therapy.  
  • Polycythaemia vera (PV), a disease in which too many red blood cell precursors and erythrocytes (red blood cells) are made in the bone marrow. The increased production of red blood cells occurs independently of the body's usual control mechanisms. Almost all PV cases have a mutation of the Janus 2 kinase gene (JAK2 mutation) at a particular point in the gene labelled V617F. JAK2 is a tyrosine kinase, when the V617F mutation occurs its activity does not switch off normally and production of red cells increases unchecked. When RBCs build up in the blood stream, they can cause the spleen to swell. Itchiness occurs, especially in warm water and there may be changes in the skin colour. The most serious problem is the excess red blood cells can make the blood thicker, which can increase the risk of inappropriate clotting (thrombosis) in both the veins and arteries. This may result in a stroke or clots causing damage to vessels and important organs of the body. Polycythaemia vera is also called primary polycythaemia. A variety of other factors can cause increased red blood cell production; for instance, long-term exposure to low concentrations of oxygen. These increases in RBCs are referred to as secondary polycythaemia. Diagnosis is usually made following a routine examination where an increase in red blood cells (polycythaemia) or haemoglobin is found. The patient’s medical history is checked and other investigations may be performed to distinguish between primary and secondary polycythaemia. The JAK2V617F mutation can be looked for in the peripheral blood and a bone marrow biopsy is usually required to complete the diagnosis. Management is aimed at reducing the red cell volume and the risk of thrombosis. In the first instance this is usually done by the patient donating blood (venesection) and the use of aspirin if there are no contraindications. 
  • Essential thrombocythaemia (ET), characterised by an increased number of megakaryocytes, precursor to platelets. About half (50%) of ET cases have the mutation of the Janus 2 kinase gene, JAK2V617F. Platelets change shape and become ‘sticky’ during the clotting process. This characteristic allows them to plug holes in leaking blood vessels, but excess platelets and platelet clumping can make it hard for the blood to flow normally and can increase a person’s risk of developing inappropriate blood clots, a stroke or heart disease. Diagnosis is made by firstly distinguishing ET from secondary thrombocytosis – increased numbers of platelets caused by non-marrow disorders such as iron deficiency, rheumatoid arthritis, bleeding or removal of the spleen. The JAK2V617F mutation can be looked for in the peripheral blood cells and a bone marrow biopsy is usually required to complete the diagnosis. Management of ET is aimed at reducing the risk of the disease. This includes ensuring that patients have their cardiovascular risk factors managed including blood pressure management, stopping smoking, cholesterol control and preventing or managing weight problems and diabetes. Aspirin is usually recommended if there are no contraindications. Tablet based chemotherapy to reduce the platelet count may be used in some patients.
  • Primary myelofibrosis (PMF) is a disease characterised by overproduction of megakaryocytes (platelet precursors) and precursors of mature red blood cells and white blood cells in the bone marrow. In the fully developed disease this is also associated with deposits of fibrous connective tissue in the bone marrow. About half (50%) of PMF cases have the mutation of the Janus 2 kinase gene, JAK2V617F. The dense network of fibre inhibits the normal formation and maturation of RBCs and myelocytes. The red blood cells that do enter the bloodstream are often malformed, looking like teardrops instead of circles. There may be too few normal mature red blood cells to carry oxygen, causing anaemia. Fibre cells may also spread to the spleen. The spleen and liver may become enlarged as a result. A bone marrow biopsy is required to diagnose PMF. Management of PMF includes support with transfusions of red blood cells and in younger patients consideration for a bone marrow transplant from a donor (often a relative).  
  • Other rare disorders: chronic neutrophilic leukaemia; some types of chronic eosinophilic leukaemias and mastocytosis

MPNs are not curable, but their slow progression can usually be controlled and their symptoms alleviated. For each, there is a slight chance that the disease will develop into an acute leukaemia. If this occurs, the course of the disease will be accelerated, the symptoms will intensify, and more aggressive treatment will be required.

Signs and symptoms

The severity of a MPN varies from patient to patient. The condition may be acute and life-threatening or it may be very subtle, existing for years before being diagnosed, frequently during a routine physical examination. While each condition has its own set of symptoms, they also have many in common, including:

  • Weakness and fatigue
  • Weight loss
  • Enlargement of the spleen (splenomegaly) - cells accumulate in the spleen because it makes blood cells and because it filters old or abnormal cells out of the bloodstream. This causes the spleen to swell, which can cause abdominal discomfort.
  • Bleeding and bruising, due to insufficient and/or abnormal platelets
  • Night sweats
  • Bone and joint pain
  • Pallor due to anaemia (when red blood cells are decreased not increased)
  • Frequent infections

In someone with PV, the excess number of RBCs produced increases the volume and thickness (viscosity) of the blood. This can cause symptoms such as headaches, dizziness, visual distortion, itching, and paraesthesia (numbness and tingling). Sometimes the excessive RBCs may lead to complications, such as: stomach ulcers, kidney stones, venous thrombosis (blood clots), stroke, and rarely, to congestive heart failure.

Primary Myelofibrosis, which occurs most frequently in those over 60 years of age, often causes no symptoms early in the course of the disease - about 1/3 of those who are diagnosed are asymptomatic. Those patients who do have symptoms may experience fatigue, shortness of breath and splenomegaly. Fibrous tissue eventually fills the bone marrow, reducing the production of all blood cells. Anaemia may become severe with this MPN.

Most people with essential thrombocythaemia are asymptomatic, but some develop thrombosis or haemorrhage because of increased numbers of dysfunctional platelets. This may cause tingling in the hands and feet, headaches, weakness, dizziness, nosebleeds and easy bruising.


Laboratory tests

Full blood count (FBC) and differential
FBCs and differentials are the most frequently ordered tests used to help diagnose and monitor MPNs. Often ordered as part of a yearly physical examination, they are routine tests that count the number and relative proportion of each of the different types of cells in your blood stream. They give your doctor information about the size, shape and relative maturity of the blood cells present in your blood at that moment.

Typically, the body produces and destroys all cells in a balanced manner, and conditions where a cell type is over – or under-expressed are considered abnormal. In MPNs, if the production of a cell type outpaces its destruction (or vice versa) by the body, the cell count can either increase or decrease. Disease progression changes the elevated and/or decreased numbers of blood cells. FBCs and differentials can be used to detect WBC, RBC and platelet increases, decreases, and abnormalities. They can help determine their severity, diagnose their cause, monitor the course of a disease, and monitor the response to treatment.

In polycythaemia vera, increased RBCs, platelets, and sometimes WBCs, may be seen. A high haematocrit (Hct, the percentage of RBCs in the total blood volume) may indicate relative polycythaemia (caused by a decreased amount of fluid in the blood). With myelofibrosis, immature granulocytes, and misshapen immature teardrop shaped red blood cells are often seen and WBC and RBC numbers are often decreased. In essential thrombocythaemia (ET), greatly increased numbers of platelets are seen along with: abnormally large platelets, platelet clumps and fragments of megakaryocytes.

Irregularities in cell counts may be due to MPNs, but they may also be due to a variety of other temporary or chronic conditions. Other testing is usually done to confirm or rule out the diagnosis of an MPN.

Bone marrow aspiration/biopsy
If your doctor suspects a bone marrow disorder, they may order a bone marrow aspiration and biopsy to collect a small sample of marrow. When a specialist (a pathologist, oncologist or haematologist) examines the bone and fluid from the bone marrow sample under the microscope, they can see the number, size and shape of precursor cells (blasts), red and white blood cells, and megakaryocytes (platelet precursors). They can determine the proportions of mature and immature cells, see any overgrowth of fibrous tissue, and detect any cancer cells from cancers that may have spread to the marrow. Most bone marrow disorders can be diagnosed during this examination.

For more detail on this test, see bone marrow aspiration and biopsy.

Other testing that is sometimes done includes:

ABGs (arterial blood gases) - This test measures the amount of gases in your arterial blood and may be done when polycythaemia vera is suspected. Low levels of oxygen are associated with secondary polycythaemia.

Erythropoietin is a hormone that stimulates the bone marrow to produce RBCs. With primary polycythaemia, erythropoietin levels will be very low or absent, but with secondary polycythaemia they will be normal or high.

Genetic testing is sometimes used to check for the presence or absence of a Philadelphia (Ph') chromosome or a BCR-ABL translocation, and the JAK2V617F mutation. These can be performed on both peripheral blood and bone marrow tissue.

Non-laboratory tests

X-rays and other imaging scans are sometimes used to look for signs of disease such as masses of cells in the chest, spleen or liver.


MPNs are usually not preventable or curable. The goal of MPN treatment is to slow the progression of the disease and to alleviate the symptoms and complications brought on by excessive, insufficient and dysfunctional blood cell production. 

CML is treated with a specialised small molecule drugs called tyrosine kinase inhibitor which bind specifically to the BCR-ABL tyrosine kinase and stop it working. Imatinib (also known by its trade name as Glivec®) is the drug that most patients are started on when they are diagnosed with CML. Measurements of the BCR/ABL gene with a blood test are used to monitor the effectiveness of therapy. These drugs have been used in routine treatment since the late 1990’s early 2000’s. It is still too early to tell but there is hope that at least some patients will be cured with this therapy.

With polycythaemia vera (PV), frequent venesections, the removal of units of blood, are used to decrease the number of RBCs and to decrease the blood volume (haematocrit). Once RBCs have been lowered as close to normal limits as possible, the person is monitored, and occasional venesection are used to keep the levels under control. Splenomegaly, the enlargement of the spleen, and itching may persist and the person may develop symptoms of iron deficiency. 

The risk of thrombotic complications such as strokes, heart disease and clots in the body is usually managed with aspirin in patients with both PV and ET. If patients have a history of clots or stroke they may need management with other anticoagulant medication such as warfarin.

In addition to venesections, hydroxyurea, a chemotherapy drug, may be given to decrease the number of cells produced in both ET and PV. If a suitable donor is available, a bone marrow transplant may offer a potential cure for myelofibrosis in some younger patients.

Frequent blood transfusions may be necessary to address anaemia, and surgical removal of the spleen may be required if it becomes too swollen (this may happen with any of the MPNs).


Related Pages

On this site
Tests: FBC, differential, blood gases, bone marrow aspiration and biopsy
Conditions: bone marrow disorders, anaemia, leukaemia, haemochromatosis, lymphoma

Elsewhere on the web
Leukaemia Foundation (Australia)
InsideRadiology: a resource produced especially for health consumers
The Leukemia and Lymphoma Society (US)
Aplastic Anemia & MDS International Foundation (US)
OncoLink (US)
MPN Research Foundation (US)
MPN Education Foundation (US)
MedlinePlus Medical Encyclopedia:
   Bone marrow biopsy
   Bone marrow aspiration
   Bone marrow transplant