About myeloproliferative neoplasms (MPN)
Myeloproliferative neoplasms (MPNs) are a group of chronic blood cancers. They begin in the bone marrow, where blood cells are produced. In MPNs, the bone marrow creates too many red blood cells, white blood cells, and/or platelets. This can affect blood thickness, reduce bone marrow function, or cause bone marrow scarring (fibrosis). These conditions are complex; they are caused by acquired mutations in stem cell DNA.
MPNs increase the risk of both bleeding and serious blood clots, including heart attacks or strokes. Managing cardiovascular risk factors (like high blood pressure, cholesterol, diabetes and stopping smoking) is important.
MPNs are classified by the dominant blood cell type that is affected. The three main “classic” MPNs are:
- Polycythaemia vera (PV) – overproduction of red blood cells
- Essential thrombocythaemia (ET) – too many platelets
- Myelofibrosis (MF) – scarring in the bone marrow
Other types include:
- Chronic myeloid leukaemia (CML)
- Chronic neutrophilic leukaemia (CNL)
- Chronic eosinophilic leukaemia (CEL)
- Juvenile myelomonocytic leukaemia (JMML)
- MPN, not otherwise specified (MPN-NOS)
Who gets MPN?
- 1900 Australians are diagnosed each year
- 74% of people diagnosed are over 60 years of age
- 69 years is the average age at diagnosis
Causes of myeloproliferative neoplasms (MPN)
The exact cause of MPN is usually unknown. Gene mutations in cells can occur naturally throughout life, even before birth. While the body has ways to repair or manage these changes, some mutations can escape these controls. This increases with age, making MPN more common in older adults.
Key Gene Mutations Linked to MPN – most MPNs are driven by one of three mutations:
- JAK2 (most common)
- CALR (type 1 or 2)
- MPL
These mutations affect how blood cells grow and divide.
Known Risk Factors for MPN:
- Age – the risk increases with age due to more frequent gene mutations or increase in the number of cells that carry the gene mutation over time.
- Environmental exposure – long-term exposure to high levels of benzene or ionising radiation may damage bone marrow cells.
- Family history – rarely, MPNs may run in families (familial clustering), often involving shared gene mutations.
- Genetic conditions – mutations linked to haemochromatosis may raise the risk of developing polycythaemia vera (PV). This is still being studied.
Symptoms of myeloproliferative neoplasms (MPN)
The symptoms of MPN may vary depending on:
- Type of MPN.
- How advanced or severe it is.
- Which blood cell types (red, white, or platelets) are abnormally high or low.
Some people may have few or no symptoms. While others experience more significant effects that can impact daily life.
Common symptoms from all MPN types:
- Fatigue and tiredness that doesn’t improve with rest
- Increased risk of blood clots (can this have a jump link to the heading below)
- Night sweats
- Itchy skin, especially after showering (aquagenic pruritus)
- Weakness
- Unexplained weight loss
- Bone or joint pain
- Difficulty concentrating
- Visual disturbances
- Bruising or bleeding
- Enlarged spleen (splenomegaly) – may cause abdominal discomfort or feeling full quickly (can this have a jump link to the heading below)
- Redness and/or burning of the face, hands, or feet
Go to MPN Alliance Australia for more information on symptoms and to download an MPN symptom score card.
Enlarged spleen and liver
In some MPNs, the bone marrow becomes scarred (fibrosis), reducing its ability to make blood cells. The spleen may compensate by producing blood cells. This leads to splenomegaly (enlarged spleen), causing:
- A feeling of fullness or discomfort in the upper left abdomen
- Feeling full after small meals
The liver may also enlarge (hepatomegaly). This can cause similar symptoms, but with discomfort on the upper right abdomen.
Blood clots and bleeding
MPNs increase the risk of blood clots (thrombosis). These can block blood vessels and lead to serious events like stroke, heart attack, or deep vein thrombosis (DVT). MPNs can also cause abnormal bleeding, especially when platelets are very high or low.
Signs of DVT (usually in the leg or thigh):
- Pain or swelling
- Redness and warmth over the area
Signs of Pulmonary Embolism (PE) – when a clot travels to the lungs:
- Sudden shortness of breath
- Chest pain
- Rapid heartbeat
- Coughing up blood
- Dizziness or light-headedness
Seek urgent medical attention if you experience symptoms of a blood clot.
Diagnosis of myeloproliferative neoplasms (MPN)
Diagnosing MPN involves a combination of symptom assessment, blood tests, and often a bone marrow biopsy. MPN symptoms like fatigue can be caused by many conditions, so multiple tests may be needed to confirm the diagnosis and specific type of MPN.
Medical history & physical exam
Your treatment team will:
- Review your past and current medical conditions
- Ask about infections, clotting or bleeding issues
- Record medications (prescription, over the counter, and supplements)
- Perform a physical exam to check for signs of MPN
Blood tests
Full Blood Count (FBC)
Measures the number of red blood cells, white blood cells, and platelets. Abnormal counts may suggest an MPN.
Genetic and molecular blood tests
These tests identify specific mutations or changes in your DNA that help classify the MPN and guide treatment:
- Polymerase Chain Reaction (PCR) – Detects known gene mutations
- Next Generation Sequencing (NGS) – Screens for multiple mutations at once (e.g., using an MPN gene panel)
Common gene mutations linked to MPN:
- JAK2 – found in most cases of PV and many cases of ET or MF. The JAK2 gene helps control how many blood cells your body makes. The JAK2 mutations involved in myeloproliferative neoplasms are the JAK2 V617F mutation (around 95% of PV patients have this) and the JAK2 exon 12 (about 2-5% of PV patients).
- CALR – associated with ET and MF
- MPL – mostly found in ET and MF
Knowing your gene mutation helps guide treatment and prognosis.
Blood chemistry tests
These tests help assess organ function and disease activity.
| Test | What It Shows |
| Iron studies | Iron levels and iron stores |
| Liver function tests (LFTs) | Liver health |
| Uric acid | Cell turnover and kidney function |
| LDH (Lactate Dehydrogenase) | Cell damage or disease activity |
| Erythropoietin (EPO) | Bone marrow stimulation of red cell production |
| Hepatitis/HIV screening | Important before starting some treatments |
| Antibody levels | Infection risk and immune function |
Bone marrow biopsy
If MPN is suspected, a bone marrow biopsy may be done to:
- Examine the structure and activity of your bone marrow
- Check for fibrosis (scarring) or abnormal blood cell development
- Help diagnose which type of MPN you have and to provide a baseline for monitoring. It is a key test to diagnose ET or MF.
Other tests
Depending on your situation, you may need:
- Imaging scans (e.g. ultrasound, CT) to assess spleen or liver size
- Coagulation tests (blood test) if you have bleeding problems or very high platelets
- Additional blood tests during diagnosis and treatment to track your progress over time
Your initial test results help set a baseline, so your treatment team can monitor how your condition responds to treatment and changes over time.
Types of myeloproliferative neoplasms (MPN)
There are three main types of myeloproliferative neoplasms. These are sometimes referred to as ‘Classic MPNs’.
Classic MPNs
These are the three most common MPN types:
Polycythaemia vera (PV)
What it is:
- Overproduction of red blood cells (causing high haematocrit and haemoglobin).
- Often white cells and platelets are also elevated.
Main risks:
- Blood clots
- Stroke
- Heart attack
Symptoms may include:
- Headaches
- Dizziness
- Fatigue
- Itching (especially after showers)
- Red skin (face, hands, feet)
- Burning in the hands/feet/face
- Blood clots
- Abnormal bleeding
- High blood pressure
- Abdominal discomfort (due to an enlarged spleen)
Possible progression:
- Can transform into post-PV myelofibrosis or rarely into acute myeloid leukaemia (AML)
Treatment:
- Venesection (removing blood to reduce red cell count which reduces blood thickness)
- Blood-thinning medications
- Cytoreductive therapy to reduce blood cell production
Essential thrombocythaemia (ET)
What it is:
- Overproduction of platelets in the bone marrow.
Main risks:
- Blood clots
- Abnormal bleeding
- Stroke
Symptoms may include:
- Fatigue
- Headaches
- Visual problems
- Redness, tingling or burning in hands/feet/face
- Blood clots (in lungs, legs, or abdomen)
- Bleeding if platelet count is extremely high or low
Possible progression:
- Can change into post-ET myelofibrosis or, rarely, AML.
Treatment:
- Watch and wait
- Blood-thinners
- Cytoreductive therapy or immunomodulatory therapy to reduce platelet counts
Primary myelofibrosis (PMF)
What it is:
- Scar tissue builds up in bone marrow, interfering with normal blood cell production.
World Health Organization (WHO) subtypes:
- Early/prefibrotic PMF
- Overt (fibrotic) PMF
Symptoms may include:
- Fatigue
- Weight loss
- Night sweats
- Fever
- Enlarged spleen or liver
- Anaemia
- Bruising/bleeding
- Bloods clots
- Infections
- Abdominal discomfort
Potential progression:
- 10–20% may develop AML.
Treatment:
- JAK inhibitors and cytoreductive therapy
- Transfusions
- Splenectomy (rare)
- Stem cell transplant (for eligible patients)
Post-ET or post-PV myelofibrosis
Sometimes people with essential thrombocythemia (ET) or polycythemia vera (PV) can develop myelofibrosis (MF) over time. This is called post-ET or post-PV myelofibrosis, treatment is the same as primary myelofibrosis (PMF).
Other types of MPNs
Chronic myeloid leukaemia (CML)
What it is:
- An MPN caused by the Philadelphia chromosome (BCR-ABL gene fusion).
For more information go to Chronic myeloid leukaemia
Chronic neutrophilic leukaemia (CNL)
What it is:
- Rare MPN marked by the overproduction of neutrophils
Prognosis:
- Often progresses slowly but can become aggressive within 2 years.
Symptoms may include:
- Fatigue
- Night sweats
- Bone pain
- Weight loss
- Easy bruising
- Enlarged spleen/liver
Treatment:
- No standard therapy, management focused on symptoms.
- There is ongoing research into targeted treatments.
Chronic eosinophilic leukaemia (CEL)
What it is:
- Overproduction of eosinophils (another type of white blood cell).
Symptoms depend on where eosinophils accumulate:
- Fever
- Cough
- Fatigue
- Muscle pain
- Diarrhoea
- Swelling around face/throat
- Itching
Treatment options:
- Corticosteroids
- Immunotherapy
- Cytoreductive therapy
- Targeted therapy
- Chemotherapy (if progressed)
- Stem cell transplant may be considered
Juvenile myelomonocytic leukaemia (JMML)
What it is:
- A rare MPN that affects young children, often under 4 years old.
Associated with:
- Genetic syndromes like Noonan syndrome or neurofibromatosis.
Symptoms:
- Enlarged spleen and liver.
Treatment:
- Stem cell transplant is the main treatment with a curative aim.
MPN – not otherwise specified (MPN-NOS)
What it is:
- An MPN that doesn’t fit clearly into another subtype.
Symptoms and treatment:
- Vary depending on individual disease features.
Related conditions: MDS/MPN overlap syndromes
These rare conditions share features of both MPNs and Myelodysplastic Syndromes (MDS). Which may include both overproduction and dysfunction of blood cells.
MDS/MPN Subtypes Include:
- Chronic myelomonocytic leukaemia (CMML)
- MDS/MPN with neutrophilia
- MDS/MPN with SF3B1 mutation and thrombocytosis
- MDS/MPN, not otherwise specified
Transformation risk
While many MPNs are stable for years, some may transform over time into:
- Another type of MPN (ET to MF, ET to PV, PV to MF)
- Acute Myeloid Leukaemia (AML) – all MPNs have a slight risk of transforming to AML but this more commonly occurs from PMF
- Myelodysplastic Syndromes (MDS)
Prognosis of myeloproliferative neoplasms (MPN)
The prognosis is an estimate your haematologist will make of the likely course and outcome of your disease. In MPN your haematologist will discuss the risks of complications from the disease:
- The risks of vascular or thrombotic (clotting) events.
- The risk of progression and transformation of the disease.
Your haematologist will consider many factors when discussing your prognosis. Some of these are the type of MPN you have, your age, and your overall health, including your cardiovascular risk factors. MPNs are considered a chronic blood cancer and patients may well have a close to normal life expectancy.
Treatment of myeloproliferative neoplasms (MPN)
MPNs are usually not curable, treatments can help control symptoms, reduce risks, and improve quality of life. Stem cell transplant is the only known potential cure for some types of MPN.
Treatment Goals:
- Lower high blood counts to reduce the risk of complications (like blood clots and bleeding)
- Improve symptoms and day-to-day wellbeing
- Manage cardiovascular risk factors (stop smoking, manage weight, cholesterol, diabetes and high blood pressure)
- Help you live your best and longest life
Watch and wait (active monitoring)
If you’re not experiencing symptoms or have low-risk disease you may not need immediate treatment. Instead, your doctor will monitor your health and blood counts through regular check-ups.
You may also be prescribed low-dose aspirin to help reduce clotting risks.
Standard therapies
These are the most commonly used treatments for MPN:
Aspirin
- Taken daily to reduce blood clot risk
- Makes platelets less “sticky” but doesn’t lower their number
Venesection (Phlebotomy)
- Blood is drawn (like donating) to reduce red blood cell count which reduces blood thickness
- Usually used in polycythaemia vera (PV)
Cytoreductive therapy
Used to reduce the number of blood cells produced.
Hydroxycarbamide (Hydroxyurea)
- Daily capsule
- Possible side effects: Anaemia, nausea, skin conditions (including increased risk of skin cancer), diarrhoea or constipation
Pegylated interferon
- Long-acting injection (weekly or often less frequently over time)
- Preferred in younger people or those planning pregnancy
- Increasingly used in people of all ages
- Possible side effects: Flu-like symptoms, fatigue, appetite loss, depression
Anagrelide
- Lowers platelet count (mainly used in ET)
- Taken as a capsule
- Not currently funded on the PBS (Australia)
- Possible side effects: Cardiac – increased heart rate, shortness of breath
- Must not be stopped suddenly
Targeted therapy (JAK Inhibitors)
These block abnormal signals that cause blood cells to grow too much. They’re often used in myelofibrosis and other high-risk MPNs.
Ruxolitinib
- Tablet taken daily
- Helps reduce spleen size and symptoms
- Possible side effects: Anaemia, low platelets, headaches, dizziness, increased risk of skin cancers
Momelotinib
- For myelofibrosis with anaemia
- Possible side effects: Low platelets, infections, nausea, diarrhoea, increased risk of skin cancers
Imatinib
- Used in chronic eosinophilic leukaemia (CEL)
- Blocks faulty BCR-ABL1 gene signals
Supportive care
Helps manage symptoms and side effects but doesn’t treat the cancer directly.
Transfusions
- Red blood cell transfusions: for anaemia and fatigue
- Platelet transfusions: for bleeding caused by low platelets
Growth factors
- Encourage bone marrow to make more blood cells
- Given as injections under the skin
- May cause flu-like symptoms or bone pain
Antibiotics
- When your white cells are low, you are at high risk of developing an infection
- Antibiotics (often IV) may be used
Vaccines
- Important to reduce infection risk
- Inactivated (non-live) vaccines
- Always check with your doctor first
Side effects of treatment
Treatment affects people differently. You may experience:
- Anaemia (low red cells) – tiredness, breathlessness
- Thrombocytopenia (low platelets) – easy bruising or bleeding
- Neutropenia (low white cells) – higher risk of infection
You’ll have regular blood tests to monitor your health.
Stem cell transplantation
This is the only known potential cure for some types of MPN. However, it is only suitable for a small number of patients, generally younger people and with high-risk disease. Your haematologist will advise if this is right for you. Information on stem cell transplants.
Surgery – splenectomy
Surgical removal of the spleen may be considered if it’s very enlarged and causing problems. This is rare, as many people respond to JAK inhibitors that reduce spleen size.
Clinical trials
Clinical trials test new treatments or combinations of treatments. You may be offered a place in a trial by your doctor. Trials can give access to promising therapies not yet available.
Participation is voluntary, and you can withdraw at any time.
You can search current clinical trials:
Fertility
Your treatment team will advise if your treatment for MPN will affect your fertility, which is your ability to conceive or father a baby. It is important that you discuss your plans, in advance, with your treatment team, before attempting to conceive or father a child. You should also inform your treatment team as soon as you find out that you or your partner are pregnant. Certain medications, such as aspirin and interferon, can be safely continued in pregnancy. However, some medications are not considered safe in pregnancy and should be discontinued. Patients with MPNs are at higher risk of pregnancy-associated complications and will require closer monitoring in pregnancy. Many patients with MPN can have a successful pregnancy.
Follow up
Ongoing follow up, including frequent blood tests is important to monitor MPN. This includes all people with MPN – watch and wait and for the majority on treatment. Treatment and monitoring are likely to be ongoing for the rest of your life. It is important to manage any cardiac risk factors and your general health, also keep up to date with regular screening for other cancers like cervical, bowel, breast, prostate, lung, skin.
Living with myeloproliferative neoplasms (MPN)
How MPN affects your everyday life will depend on many factors. It could be that you are managing work, your emotional health or managing fatigue. Consider wellness activities such as yoga, aerobic activity, strength training, meditation, massages, support groups, and improved nutrition. An international study of a large number of MPN patients showed wellness activities improved symptoms, including fatigue and depression. It also found these activities improved the quality of life for MPN patients (The SIMM study).
There are some helpful resources and information to guide you – Living well with blood cancer. The Online Blood Cancer Support Service has learn modules on cancer related fatigue, emotional resilience and more.
Caring for someone with myeloproliferative neoplasms (MPN)
We have a range of information and resources that may help when you are caring for someone with myeloproliferative neoplasms (MPN).
References
- Current myeloproliferative neoplasm scoring systems for clinical practice | Blood | American Society of Hematology
- The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms
- Evolution of WHO diagnostic criteria in “Classical Myeloproliferative Neoplasms” compared with the International Consensus Classification | Blood Cancer Journal
- How I approach the treatment of thrombotic complications in patients with myeloproliferative neoplasms | Blood | American Society of Hematology
- Myeloproliferative neoplasms – ScienceDirect
- Myeloproliferative Neoplasms – StatPearls – NCBI Bookshelf
- MPL (Myeloproliferative leukaemia) mutation | Pathology Tests Explained
- Myelofibrosis – Symptoms, diagnosis and treatment | BMJ Best Practice
- The Classification of Myeloproliferative Neoplasms: Rationale, Historical Background and Future Perspectives with Focus on Unclassifiable Cases – PMC
