Chronic myeloid leukaemia is a type of blood cancer called a myeloproliferative neoplasm. It is defined by an abnormal fusion gene called BCR::ABL1. This gene causes the bone marrow to produce too many white blood cells, especially myelocytes and neutrophils, which normally help fight infection. Most people are diagnosed at an early, slow-growing stage called the chronic phase.
Where is chronic myeloid leukaemia found?
In the chronic phase, the abnormal cells are mainly found in the blood and bone marrow. The spleen and liver often become enlarged because they trap excess blood cells. In the blast phase, which is a more advanced stage, immature cancer cells called blasts can spread outside the bone marrow to areas such as the lymph nodes, skin, soft tissues, liver, and spleen.
What are the symptoms of chronic myeloid leukaemia?
Some people have no symptoms, and the diagnosis is made after a routine blood test shows a high white blood cell count. When symptoms do occur, they often develop gradually. They may include fatigue, weakness, weight loss, night sweats, anemia, and a feeling of fullness in the upper left abdomen due to an enlarged spleen.
If untreated, chronic myeloid leukaemia usually becomes more aggressive over time. Symptoms may worsen and include fever, increased fatigue, worsening anemia, low platelet counts, very high white blood cell counts, and progressive enlargement of the spleen.
How common is chronic myeloid leukaemia?
Chronic myeloid leukaemia affects about 1 to 2 people per 100,000 each year worldwide. It can occur at any age but is more common in older adults. Because modern treatments are very effective, many people now live long lives with this disease, and the number of people living with chronic myeloid leukaemia continues to increase.
What causes chronic myeloid leukaemia?
For most people, the cause is unknown. High-dose radiation exposure has been linked to an increased risk. Unlike some other blood cancers, chronic myeloid leukaemia is rarely inherited.
What is the BCR::ABL1 fusion gene, and why is it important?
Chronic myeloid leukaemia is caused by a swap of genetic material between chromosomes 9 and 22. This change creates the BCR::ABL1 fusion gene and a shortened chromosome 22 called the Philadelphia chromosome.
The BCR::ABL1 fusion gene produces an abnormal protein that sends constant growth signals to blood-forming cells. This discovery led to the development of targeted medicines called tyrosine kinase inhibitors, which block the abnormal signal. These drugs are highly effective, especially when treatment begins in the chronic phase.
What are the disease phases of chronic myeloid leukaemia?
Chronic myeloid leukaemia is now considered a two-phase disease.
- Chronic phase: The chronic phase is the earliest stage and the one in which most people are diagnosed. The disease grows slowly, and treatment is usually very effective.
- Blast phase: The blast phase is an advanced stage in which immature cells called blasts account for 20% or more of the cells in the blood or bone marrow. The blast phase behaves like acute leukaemia and is much harder to treat.
You may also see the term chronic phase with high-risk features. This refers to chronic-phase disease that shows findings linked to a higher risk of progression or resistance to treatment, such as rising blast counts, very high basophils, or additional chromosomal changes.
How is the diagnosis made?
The diagnosis of chronic myeloid leukaemia is made using blood tests, genetic testing, and often a bone marrow biopsy. These tests help confirm the diagnosis (presence of the BCR::ABL1 fusion gene) and determine the disease phase.
Blood tests and peripheral blood findings
A complete blood count usually shows a very high white blood cell count. The increase is mainly due to neutrophils and neutrophil precursors, meaning neutrophils at different stages of development. Cells called myelocytes and segmented neutrophils are often especially increased.
Basophils and eosinophils, which are other types of white blood cells, are commonly increased. Blasts are usually very low in the chronic phase, typically less than 2 percent. Platelet counts may be normal or high, and anemia is common.
When a blood smear is examined under the microscope, doctors see many white blood cells at different stages of maturation, rather than just mature cells. Importantly, these cells should look normally formed, without abnormal shapes that suggest a different bone marrow disorder.
In the blast phase, blood tests often show a rising number of blasts. These immature cells may appear suddenly and in large numbers, sometimes with a drop in normal blood cells such as red cells and platelets.
Bone marrow biopsy findings
A bone marrow biopsy is often performed at diagnosis to confirm the disease phase and provide a baseline for comparison during follow-up.
In the chronic phase, the bone marrow is usually very cellular, meaning it is crowded with blood-forming cells. There is marked expansion of granulocytes, the family of cells that includes neutrophils, at all stages of development. Red blood cell precursors are often reduced. Megakaryocytes, the cells that make platelets, are often increased and may appear smaller than usual with simpler, less lobulated nuclei. Mild scarring of the bone marrow may be present in some people, but it does not by itself predict treatment response.
In the blast phase, the bone marrow shows a marked increase in blasts. These blasts may form large sheets that replace normal bone marrow tissue. The blast phase can be myeloid, lymphoid, or, rarely, mixed, meaning the blasts may resemble those seen in acute myeloid leukaemia or acute lymphoblastic leukaemia. In some cases, the blast phase first appears outside the bone marrow, such as in the skin or lymph nodes.
Genetic tests
Genetic testing is essential because the presence of the Philadelphia chromosome or the BCR::ABL1 fusion gene defines chronic myeloid leukaemia.
Chromosome testing, also called cytogenetics or karyotyping, looks directly for the exchange of genetic material between chromosomes 9 and 22 and can also detect additional chromosome changes that may affect risk.
FISH testing uses fluorescent probes to identify the BCR::ABL1 fusion inside cells and is helpful when the Philadelphia chromosome is not clearly seen on routine chromosome testing.
Molecular testing uses a method called RT-PCR to detect and measure the amount of BCR::ABL1 genetic material. Results are reported on an international scale as a percentage called BCR::ABL1IS. This test is used both at diagnosis and during follow-up to monitor treatment response.
The report may also describe the type of BCR::ABL1 transcript present. Most people have one of two common types called e13a2 or e14a2. These transcript types usually remain stable over time.
If the disease does not respond as expected to treatment, additional testing may be performed to identify mutations in the BCR::ABL1 kinase domain. These mutations can explain resistance to specific targeted therapies and help guide treatment choices.
What happens after the diagnosis?
After the diagnosis is confirmed, treatment usually begins with a tyrosine kinase inhibitor. Regular blood tests and molecular testing are used to monitor how well the disease is responding. Over time, doctors look for improvement in blood counts, disappearance of the Philadelphia chromosome, and a steady drop in BCR::ABL1 levels.
Most people treated in the chronic phase respond very well and can live long, active lives. Some people who achieve a deep and stable molecular response may eventually be candidates for carefully supervised treatment discontinuation, known as treatment-free remission.
What is the prognosis for a person with chronic myeloid leukaemia?
In the modern era, prognosis is strongly influenced by the extent to which the disease responds to tyrosine kinase inhibitor therapy.
Doctors monitor response at three levels:
- A hematologic response means the blood counts return toward normal.
- A cytogenetic response means the Philadelphia chromosome is no longer detected in dividing cells by chromosome testing.
- A molecular response means the level of BCR::ABL1 measured by RT-PCR drops significantly. Results are reported on the international scale and are used to track progress over time. Many people achieve a deep molecular response, meaning the BCR::ABL1 level becomes extremely low. If this deep response remains stable for at least a year, some people may be able to stop treatment under careful medical supervision. About half of those people can stay off treatment long term. This is called treatment-free remission.
Risk scores based on age, spleen size, and blood counts at diagnosis can also help predict response to therapy. Overall, most people treated in the chronic phase do very well, with high long-term survival rates. The blast phase remains challenging to treat and has a much less favorable prognosis.
Questions to ask your doctor
- What phase of chronic myeloid leukaemia do I have?
- Was the Philadelphia chromosome or BCR::ABL1 fusion found in my testing?
- What do my blood smear and bone marrow biopsy results show?
- How will my response to treatment be monitored over time?
- What does my BCR::ABL1IS result mean?
- Do I have any high-risk features that affect my prognosis?
- Could treatment-free remission be an option for me in the future?
