Chronic myeloid leukaemia, also known as chronic myelogenous leukaemia or CML, is a rare cancer that affects bone marrow and white blood cells. Our bodies are constantly making new blood cells but in CML too many white blood cells are produced that cannot develop properly. Thanks to international cancer research, we know quite a lot about how CML develops and what some risk factors are, but the exact cause of CML in most patients is still not fully understood.
Is chronic myeloid leukaemia curable?
Treatment for CML is one of the biggest success stories in cancer research to date, with a group of targeted drugs called tyrosine kinase inhibitors that were approved for use in 2001 completely transforming survival rates. Historically, 10 year survival rates for CML were as low as below 20% but this number has since increased to over 80%.
Tyrosine kinase inhibitors stop CML cells from being able to grow and divide, though patients generally need to take the medication for the rest of their lives to avoid relapse. In recent years some patients have successfully stopped treatment and remained in remission, but this is rare.
A small proportion of patients can also face treatment resistance where the drug becomes less effective at stopping the cancer cells and the CML starts growing again. That is why it is still crucial for cancer research to continue worldwide to try and make these drugs more effective and help us reach a day where no life is cut short by this disease.
Causes, symptoms, diagnosis and treatment:
What causes chronic myeloid leukaemia?
CML is slightly more common in male patients and older people. The average age at diagnosis is 66 with 70% of patients being 55 or older. The only known environmental risk factor is exposure to high-dose radiation. This is quite uncommon though.
There is also a mutation found in the DNA of up to 95% of CML patients, which researchers believe could be driving cancer growth. Scientists still do not really know why this mutation happens, it is often seemingly random. This mutation is called the Philadelphia chromosome.
The swapping in the Philadelphia chromosome means that two sections of DNA are suddenly next to each other when they would not normally be. They form the cancer causing BCR-ABL oncogene which sends signals telling cells to grow. Usually BCR-ABL is really strictly regulated to control cell growth, but the mutation means BCR-ABL is stuck in active mode and is telling cells to keep growing.
What are the symptoms of chronic myeloid leukaemia?
Symptoms of CML are quite vague and often develop gradually or don’t present until later stages of the disease. CML is more often diagnosed through routine blood tests before symptoms present and some countries have documented around 50% of patients are asymptomatic at diagnosis.
When patients do experience symptoms, common ones include:
Feeling more tired than usual
Loss of appetite or weight without trying
Bleeding or bruising more easily than usual
Night sweats
Headaches
Getting ill more often and taking longer to recover
Swollen glands
Swollen tummy or discomfort under the ribs from an enlarged spleen
There are also some less common symptoms such as blurred vision or swollen joints.
How is chronic myeloid leukaemia diagnosed?
There are usually a lot of tests done to diagnose CML. Often a GP might suspect something from the results of a routine blood test as patients may not come in with symptoms. The main way a CML diagnosis can be confirmed is by establishing the presence of the mutation called the Philadelphia chromosome, found in up to 95% of CML cases.
If a patient is seen first by their GP they may have a few different tests done:
Physical Examination - you may lie or sit down and the doctor checks for any abnormalities in the skin like bruising, swelling or infection.
Blood tests – to check the function of important organs such as your liver and kidneys. They also look at abnormal blood cell counts as a key sign of leukaemia.
If the GP is worried about CML they will refer the patient to a specialist called a haematologist. This is a doctor who specialises in blood diseases. The specialist will perform a few more tests to be sure of the diagnosis:
Gene tests - FISH (fluorescence in situ hybridisation) is a test that looks at changes in genes. This technique dyes the Philadelphia chromosome mutation yellow. If it is present in the patient's sample, it will fluoresce under a special microscope.
Bone marrow test – These are used to understand what type of CML cells are present. This is usually done through two different techniques at the same time; Bone marrow aspiration means they draw bone marrow liquid up into a syringe. Bone marrow trephine biopsy means they remove 1-2cm long core of bone marrow in one piece. Both samples tend to be taken from the back of the hip. Doctors will do both tests so they can see cells in detail as well as their structure in the bone marrow.
How is chronic myeloid leukaemia treated?
The main treatment option for CML is currently a range of targeted drugs called tyrosine kinase inhibitors (TKIs). TKIs work by blocking the action of BCR-ABL, the protein responsible for driving CML development.
TKIs do not necessarily cure CML but they can stop its growth and put it into long-term remission, meaning patients have the opportunity to live long healthy lives. TKIs are one of the biggest success stories from cancer research and without scientists asking those bold initial questions about how CML works, patients would not be receiving these lifesaving drugs today.
Unfortunately, a small proportion of patients experience treatment resistance. This is where the TKI treatment stops working, either as effectively, or completely. Research is ongoing worldwide to try and overcome this resistance and give patients more options. When a patient experiences treatment resistance to TKIs, the main treatment options are chemotherapy and a stem cell transplant.
What are the phases of chronic myeloid leukaemia?
Historically, the progression of chronic myeloid leukaemia has been split into three phases; chronic, accelerated and blast phase. This system is still recognised by the International Consensus Classification (ICC) system. In 2022 the World Health Organisation (WHO) changed to only classifying CML as having two phases; chronic and blast. You may hear medical teams using either of these systems.
Chronic phase
Chronic phase (CP) is the earliest stage of CML development and the most common, with 9 out of 10 patients being diagnosed with chronic phase CML. In this phase less than 10% of blood cells are the poorly specialised myeloid blast cells of CML and most of the cells found in the blood are still fully functional. In chronic phase some patients may feel unwell, but a lot have few to no symptoms.
Accelerated phase
Accelerated phase is sometimes also referred to as high risk chronic phase. If CML is left untreated it can start to develop faster and enter accelerated phase. Here 10-19% of cells in the blood and bone marrow are ‘CML myeloid blast cells’, that take up space over healthy cells. In accelerated phase patients may have more obvious symptoms like fatigue and weight loss.
Blast phase
Blast phase will sometimes also be referred to as acute phase or blast crisis. This is the most advanced phase of CML and means there are too many poorly specialised myeloid blast cells in the blood and bone marrow (more than 20%). There is therefore not enough room for the healthy cells and patients will experience more severe symptoms. Patients treated at blast phase may return back down to chronic phase.
Why is chronic myeloid leukaemia one of the greatest research success stories?
What used to be a terminal prognosis is now a mostly survivable disease. It was fully understanding how CML develops - and specifically discovery research into the Philadelphia chromosome - that unlocked game-changing treatments for CML. Survival rates for CML used to be as low as 15%, and through decades of discovery research leading to the development of targeted treatments, survival rates are now almost above 80%.
Stories like this reaffirm our mission to support and uplift the best international cancer research. We know that any new treatment for cancer starts with discovery research, with someone asking a question about cancer no one has ever asked before.
How Worldwide Cancer Research is working towards cures
Discovery research is the critical first stage of the research journey, creating a pipeline for future breakthroughs. By funding it, we can transform our understanding of how cancer works, start new cures and ultimately, reach a day when no life is cut short by cancer.
Since we were founded, Worldwide Cancer Research has spent over £16 million asking these important questions about blood cancers.
We have funded over 100 projects researching leukaemia, like Dr Azzoni and his team in Italy, who recently uncovered some of the fundamental science behind how a rare childhood blood cancer forms. But we know more research is still needed for rare leukaemias, and that’s why we continue to fund ground-breaking research into any and all cancer types.
Your chronic myeloid leukaemia FAQs:
Can chronic myeloid leukaemia be cured?
Tyrosine kinase inhibitors (TKIs) are a class of targeted drugs that have revolutionised CML survival. They do not necessarily cure CML, but they can stop its growth and put it into long-term remission, meaning patients have the opportunity to live long healthy lives.
What is a tyrosine kinase inhibitor?
The main treatment option for CML is a range of targeted drugs called tyrosine kinase inhibitors (TKIs). TKIs work by blocking the action of BCR-ABL, the protein responsible for driving CML development.
How common is CML in the UK?
CML is a rare type of cancer and less than 1% of new cancer cases in the UK are CML, with around 900 people a year being diagnosed.
What is the difference between chronic myeloid leukaemia and acute myeloid leukaemia?
Chronic myeloid leukaemia and acute myeloid leukaemia are two separate diseases that are diagnosed and treated differently. The main difference is that CML grows slowly and AML grows fast. This is reflected in their names as chronic means slow and acute means fast.
What is the Philadelphia chromosome?
Chromosomes are long structures of tightly packed DNA and every human cell has 23 pairs of chromosomes. Scientists found that in mutated CML cells, there is a mistake causing chromosomes number 9 and 22 to swap a section of their DNA.
This means part of chromosome 9 is on chromosome 22 and part of chromosome 22 is on chromosome 9. This hybrid chromosome is called the Philadelphia chromosome and is found in up to 95% of CML patients and its presence is one of the main diagnostic criteria for CML. Scientists still do not really know why this mutation happens, it is often seemingly random.
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