MDS/MPN overlap syndromes
Myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN) are types of blood cancer. MDS/MPN overlap syndromes describe a group of blood cancers which share characteristics of both MDS and MPN.
MDS/MPN overlap syndromes explained
If you have an MDS/MPN overlap syndrome, you will have a blood cancer that shares features with both myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN). We explain what each of these are below, and you can read more about them elsewhere on our website.
- Myelodysplastic syndromes (MDS). If you have MDS, your bone marrow doesn’t work properly and makes faulty myeloid stem cells. These cells are unable to develop normally into healthy blood cells. “Myelo” means bone marrow and “dysplasia” means abnormal cells.
- Myeloproliferative neoplasms (MPNs). If you have an MPN, your body products too many of a particular type of blood cell. There are three main types of MPN – essential thrombocythaemia (ET), polycythaemia vera (PV) and myelofibrosis (MF). The type you have depends on the type of blood cell your body is making too many of.
MDS/MPN overlap syndromes therefore happen when your bone marrow doesn’t work properly. It may make too many of one particular type of blood cell, and not enough of other types of blood cell.
The type of MDS/MPN overlap syndrome you have depends on the genetic changes that happen in your cells, which makes the cells behave abnormally.
Read more about your blood cells.
Types of MPN/MDS overlap syndromes
There are lots of different kinds of MDS/MPN overlap syndromes. The most common type is chronic myelomonocytic leukaemia (CMML). We have separate information on CMML.
This page provides information that is relevant to some of the other types, including:
- MDS/MPN with neutrophilia, also known as atypical chronic myeloid leukaemia (aCML)
- Clonal monocytosis of undetermined significance (CMUS)
- MDS/MPN with SF3B1 mutation (MDS/MPN-T-SF3B1)
- MDS/MPN with ring sideroblasts and thrombocytosis not otherwise specified (MDS/MPN-RS-T-NOS)
- MDS/MPN-not otherwise specified (MDS/MPN-NOS)
Who gets MDS/MPN overlap syndromes?
Around 900 people in the UK are diagnosed with an MDS/MPN overlap syndrome every year. Approximately 650 of these people will have CMML. The other types listed on this page are therefore extremely rare.
MDS/MPN overlap syndromes usually affect people aged over 65, but this isn’t always the case. They tend to be slightly more common in men.
Causes of MDS/MPN overlap syndromes
We don’t understand exactly why some people develop MDS/MPN overlap syndromes and others don’t, but we do know that all of the different types are caused by genetic changes in your stem cells. Stem cells are found in your bone marrow, and they usually develop into healthy blood cells.
In people with MDS/MPN overlap syndromes, the genetic changes cause some stem cells to be faulty. These abnormal cells don’t grow properly, and can result in you having too many of one particular type of blood cell and not enough of another kind.
Most genetic changes happen by chance during your lifetime, and aren’t inherited. This means that they are not caused by anything you did, and you did not get them from your parents. You also won’t pass them onto any children you have. Scientists are doing more research to understand these genetic changes and why they occur.
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Symptoms of MDS/MPN overlap syndromes
Signs or symptoms of MDS/MPN overlap syndromes will depend on which type you have and how it is affecting you. This includes things like whether you have high or low levels of red or white blood cells, high or low levels of platelets, or a swollen spleen or liver.
Some common symptoms and signs of MDS/MPN overlap syndromes include:
- shortness of breath
- tiredness (fatigue)
- bruising, bleeding or a rash on your skin
- pale skin (pallor)
- pain or a feeling of fullness below the ribs on the left side
- unexplained weight loss
- fever
- frequent infections.
It’s important to know that certain signs can look different on different skin tones. Paleness (pallor) can usually be detected on dark skin by pulling down on the bottom eyelid – if the skin inside your eyelid is white instead of pink, you may have pallor. On Black or brown skin, bruising or rashes may show up as purple or darker than the skin around them.
If you have one or more of the symptoms on this list, or any other unexplained symptoms that you’re worried about, speak to your GP. Symptoms of blood cancer can often be explained by other causes, but it’s important to get checked out.
Tests you might need
MDS/MPN overlap syndromes are diagnosed through testing. Your GP should send you for tests quickly if you have any symptoms of blood cancer. You can prompt them to follow the Faster Diagnosis Pathway and Jess’s Rule if you are asked to wait a long time or feel you aren’t being listened to.
Tests you may need include:
- Full blood count (FBC). Your doctor will take samples of your blood to check your full blood count. This measures the number of each type of cell in your blood: red blood cells, white blood cells and platelets.
- A bone marrow biopsy. You may need a bone marrow biopsy, where a sample of bone marrow is removed – usually from your hip.
- Genetic tests. These are tests to look for changes to the genes in your blood cells. They can help to reveal which MDS/MPN overlap syndrome you have. You may also hear genetic tests being called cytogenetic tests, FISH testing, or molecular testing.
- Other blood tests. As well as a full blood count, doctors may also do other tests on your blood to see how different blood cells are behaving, and to check how well your liver and kidneys are working.
- X-rays and scans. Doctors may also want to do tests such as an x-ray, MRI scan, or CT scan. These kind of tests allow them to see how blood cancer may be affecting your body.
Tests can also help your doctor determine what treatment you need, and how you might respond to treatment. You may have to repeat some tests after starting treatment, or after a course of treatment.
Treatment for MDS/MPN overlap syndromes
Treatment for MDS/MPN overlap syndromes aims to control the disease and manage any symptoms.
Most treatments for MDS/MPN overlap syndromes are based on treatment for MDS or MPN. The treatment you have will depend on your exact diagnosis as well as things like your age, your general health, and the effect of the disease on your spleen.
Current treatments include:
- chemotherapy
- hypomethylating agents
- targeted therapies
- immunotherapies
- rarely, a splenectomy or splenic radiation
- a stem cell transplant
- treatment as part of a clinical trial.
Doctors may also decide that you don’t need any treatment, or don’t need it yet – this is called ‘active monitoring’, also known as ‘watch and wait’. Your symptoms will be monitored and you may have regular tests, which will help your doctor to know if and when you may need to start treatment in the future.
Most treatments will not cure an MDS/MPN overlap syndrome, but some people who have a stem cell transplant may end up cured in certain circumstances. Your doctor will let you know if a stem cell transplant might be a suitable treatment option for you, and what to expect if so.
You can read more about the current available treatment options below, but remember that not every treatment will be suitable for every disease or every person with that disease. Your doctor is the best person to speak to about your treatment.
Chemotherapy can be an option if you have an MPN/MDS overlap syndrome with a high level of white blood cells or platelets. It works by destroying the blood cells, and therefore lowering the level of these abnormal cells. It can also help to shrink a swollen spleen.
A common chemotherapy drug prescribed for MPN/MDS overlap syndromes is hydroxycarbamide. This is usually given in tablet form, and most people will be able to take it at home.
If you’re recommended to have a more intense form of chemotherapy, such as a drug that needs to be given through an IV drip, you may need to go into hospital as either an outpatient or inpatient.
Some people will have chemotherapy as well as another type of treatment, for example a stem cell transplant. However, doctors will usually try other treatment methods first, if possible, as they can be less harsh on your body than chemotherapy.
If you also suffer from anaemia, medicines like hydroxycarbamide that lower blood cell levels can make the anaemia worse. This is because it also kills healthy blood cells as well as the cancerous ones. Your doctor may be able to prescribe something to help counteract this effect on the anaemia, or they may need to balance your risk of anaemia with the risk of allowing your blood cell counts to grow or remain high.
Hypomethylating agents are a type of drug that specifically target the abnormal genetic material in a cancer cell, rather than destroying the cell itself.
Decitabine and azacitidine are two hypomethylating agents that have been approved to treat some MDS/MPN overlap syndromes. They are usually given in cycles through an injection into the skin (a subcutaneous injection), or in some cases may be given through an intravenous (IV) drip in your vein. This means that you will have treatment for a period of time, followed by a period of rest, before having more treatment.
Targeted therapies for MDS/MPN overlap syndromes are aimed at something called ‘upregulated pathways’ within the cells of your body, which are constantly switched on. All of our cells have the ability to receive, process and respond to external signals, which tell the cell to do something. Upregulation is the process in which a cell increases the production of its component parts in response to such signals.
An example of a targeted therapy is a class of drugs known as JAK inhibitors. These drugs slow down cell production, and lower levels of inflammation. They can also reduce your spleen size and improve any related symptoms.
JAK inhibitors are taken daily in tablet form, but they may not be available for all people with MDS/MPN overlap syndromes. Ask your hospital team for more information about this.
Lenalidomide is an example of an immunomodulatory drug that has been successfully used to treat MDS/MPN with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T). It is taken as a tablet, and works by preventing the growth of cancer cells and stimulating your immune system to destroy them.
It can also help to improve symptoms of anaemia in some cases.
A splenectomy is a surgical procedure to wholly or partially remove your spleen. Your spleen is an organ found under the rib cage on the upper left side of your stomach (abdomen).
You may need to have a splenectomy if you suffer from swelling or enlargement of the spleen, known as splenomegaly. This happens when you have too many blood cells, as your spleen becomes overcrowded with abnormal cells and cannot work properly.
If you have a splenectomy, you may be at risk of bleeding, or at increased risk of blood clotting. You will also be at higher risk of developing infections from viruses and bacteria, as your spleen is a part of your immune system which helps your body to fight infection. We have separate information about infection, including how to prevent infections and what to do if you have one. You may also want to order our free infection alert card.
Splenic radiation therapy can sometimes be an alternative and less invasive way of shrinking the spleen. This involves having a low dose of radiotherapy on your spleen, either daily or several times a week, for a short period of time.
Allogeneic stem cell transplants are the only currently known potential cure for MDS/MPN overlap syndromes, but they won’t be suitable for everyone or every type of disease. You might be recommended this treatment if you’ve tried other options that don’t work, or if you’re at high risk of transforming into acute myeloid leukaemia (AML).
Allogeneic means that the procedure requires healthy stem cells from a donor, which are matched as closely as possible to you and transplanted into your blood stream following chemotherapy or immunotherapy. These donated stem cells will then form healthy blood cells in your bone marrow, which gradually replace the abnormal cancerous cells in your bone marrow.
Stem cell transplants are a very intensive procedure, and you’ll need to have additional treatment in the form of chemotherapy and immunotherapy to help prepare your body before the transplant. You may also need to have more treatment afterwards. Read more about allogeneic stem cell transplants in our printed booklet, which you can view online or order for free.
Clinical trials can offer the opportunity to try new treatments that are not otherwise available. They are also a way of developing new and better treatments, which is important for rarer cancers like MDS/MPN overlap syndromes.
Your doctor may suggest a clinical trial, or you might want to ask about them yourself. If there is a trial suitable for you to join, your doctor will explain more about what to expect, including any benefits or risks.
We have more information about clinical trials, including support with finding a trial.
Side effects of treatment
Treatment for MDS/MPN overlap syndromes may have side effects. Your doctor will be able to tell you more about what to look out for with the exact treatment you’re on.
If you’re worried about side effects or how they might impact you, speak to your doctor or clinical nurse specialist. You can also give our Support Service nurses a call, or read our information about coping with side effects.
If you find it hard to manage the side effects of a treatment you’re on, you may be able to take medication to help. Ask at your hospital or GP surgery if there is anything they can prescribe, or speak to a pharmacist about any over-the-counter options they can recommend.
Find out more about side effects
Tips and real stories about side effects like hair loss, peripheral neuropathy, brain fog, sleep problems, infection risk, nausea and sore mouth.
Supportive treatments
As well as any specific treatment for MDS/MPN overlap syndromes, doctors may recommend supportive treatments that can help to control your symptoms and side effects and make you feel better.
Some people may not be able to have any specific treatment for their MDS/MPN overlap syndrome, or may choose not to, but supportive treatments can still be an option.
Supportive treatment includes things like:
- Medicines to help manage pain
- Medicines to prevent or treat infections
- Medicines to prevent blood clots
- Medicines to prevent or treat anaemia
- Advice from a dietician or nutritionist
- Support with exercise or physiotherapy
- Mental health support such as counselling or therapy
- Palliative or end of life care.
You may also be worried about work and your finances, if you need to take time off to manage your disease or any symptoms or side effects. Check out our money and work pages for more information and support, including benefits you may be entitled to.
Prognosis for MDS/MPN overlap syndromes
If you have an MDS/MPN overlap syndrome, you’ll probably be wondering about what will happen in the future (your prognosis.)
Your prognosis is individual to you, and may be different from someone else you know. It will depend on things like:
- your age
- your general health and any other conditions you have
- the type of MDS/MPN overlap syndrome you have, and the exact genetic changes in your cells
- your test results
- if you need treatment, and how you respond to treatment.
The best people to ask about your prognosis are your doctor or clinical nurse specialist (CNS). They will be able to tell you more about your personal situation, and answer any questions you have.
If you’re not sure what to say, or you’re worried about anything, give our Support line a call. Our nurses can help you understand what’s going on and help you prepare to speak to your team. They can also signpost you to further support if you hear upsetting news you aren’t expecting, and recommend resources to help you explain things to your loved ones.
Transformation into acute myeloid leukaemia (AML)
Sometimes, MDS/MPN overlap syndromes can develop into a faster growing type of blood cancer called acute myeloid leukaemia (AML). This is called transformation.
Symptoms of AML and symptoms of MDS/MPN overlap syndromes are very similar. One sign of transformation into AML may be an increase in symptoms, or symptoms getting worse. It’s important to keep an eye on any symptoms you have, and report any changes to your doctor as soon as possible.
Generally speaking, around 40% (4 in 10) of people with MDS/MPN overlap syndromes will go on to develop AML. This usually happens within 5 years of diagnosis. Transformation is slightly less common than this if you have MDS/MPN with SF3B1 mutation (MDS/MPN-T-SF3B1), or MDS/MPN with ring sideroblasts and thrombocytosis not otherwise specified (MDS/MPN-RS-T-NOS).
Remember, these statistics are only averages. Your personal risk is individual to you, and will depend on lots of things including your general health and the genetic changes in your cells. If you’re worried, speak to your doctor. They will be able to tell you more about your own situation. They will also check regularly to see if you have any signs or symptoms of transformation.
We have a free booklet about acute myeloid leukaemia (AML)
Order it now, or download a PDF from our shop.
You can also visit our online information about AML to learn more.
Living with MDS/MPN overlap syndromes
Finding out you have blood cancer is never easy. It can be even harder to hear that you have a rare blood cancer like an MDS/MPN overlap syndrome, and it’s normal to feel worried or alone.
However, support is available if you need it, for you and your loved ones. There are also lots of things you can do to help you understand your condition and feel more in control. We've shared some ideas below.
Understanding your diagnosis
If you’ve just been diagnosed with an MDS/MPN overlap syndrome, you might want to:
- Read our information about what happens after diagnosis, or order our free printed booklet.
- Sign up for weekly support emails for practical tips and advice from other people with blood cancer.
- Share our information for family and friends with people you know. This contains ideas about how they can support you while looking after themselves.
- Order a free infection alert card for guidance about what to look out for and what to do if you think you have an infection. Blood cancer and blood cancer treatment can make you more at risk of infections from viruses and bacteria, so it’s important to know the signs.
Looking after your mental health
Lots of people tell us that they feel scared, angry, worried, or numb after they’ve been diagnosed with blood cancer. You may also be concerned or upset about your prognosis, and wondering how you’re going to cope with treatment.
However you feel, it’s OK, and it’s normal to have emotional ups and downs. If your worries feel like too much to cope with or if you are generally feeling low, talk to your hospital team or GP. They may be able to refer you for professional help. Or if you prefer, we have some self-help tips you can try.
Remember, your mental health is just as important as your physical health, and it deserves just as much care and attention. Don’t hesitate to give us a call or reach out via email if you need a listening ear – our Support Service Nurses will be happy to hear from you.
You may also want to visit our community forum, where you can read posts from or chat to others who understand what you’re going through.
Looking after your physical health
It’s important to eat a balanced diet and keep as active as you can when you’re living with blood cancer. This can help to lift your mood as well as keep you physically healthy before, during and after treatment.
For simple ideas to live more healthily after a blood cancer diagnosis, read our pages on eating well and staying active.
We also have a free printed booklet about eating well with blood cancer.
Your finances
You may have questions or concerns about your finances, including about any benefits you may be able to claim and your rights at work.
Cancer is classed as a disability even if you are not having treatment. So you have rights under disability laws.
For more information about this and other practical matters, read our information about money and work.
About our health information
Last full review of this information May 2026. Next full review due May 2029. We may make factual updates to the page between reviews.
We would like to thank Consultant Haematologist Dr Donal McLornan for checking the clinical accuracy of this information.
Contact our support services team
Our team of nurses and trained staff offer support and information to anyone affected by or worried about blood cancer. Contact them by phone, email, or on our Community Forum.
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