Chronic myeloid leukaemia (CML) is a rare type of blood cancer that develops when bone marrow starts producing too many abnormal white blood cells. Unlike more aggressive forms of leukaemia, CML typically progresses very slowly, and many people live with the condition for years without realizing they have it. Thanks to modern treatments, most people diagnosed with CML today can expect to live long, relatively normal lives.

Epidemiology

Chronic myeloid leukaemia is relatively uncommon compared to other cancers. In the United States, approximately 1 in 565 people will develop CML at some point in their lives. Epidemiology is the study of how diseases spread and affect populations. The disease represents about 15% of all types of leukaemia diagnosed each year.^[2]

Worldwide, the annual rate of new CML cases is about 0.87 people per 100,000, though this number increases significantly with age. People older than 70 have a higher rate, with about 1.52 cases per 100,000. In the United States specifically, between 2009 and 2013, the annual rate was 1.4 per 100,000 for women and 2.2 per 100,000 for men, showing that men are slightly more likely to develop the condition.^[7]

CML typically affects older adults, with a median age of diagnosis around 56 years. The disease usually occurs during or after middle age. While it can develop at any age, it is rare in children. Estimates for 2018 suggested there would be about 8,490 new cases of CML and approximately 1,090 deaths from the disease in the United States.^[7]

Causes

The root cause of chronic myeloid leukaemia lies in a specific genetic change that happens during a person’s lifetime, not something inherited from parents. People with CML have what’s called an acquired genetic mutation in the myeloid stem cells growing in their bone marrow. These are the cells responsible for producing certain types of blood cells.^[2]

The specific mutation that causes CML creates a new abnormal gene called BCR-ABL. This happens when parts of two different chromosomes, number 9 and number 22, break off and swap places. The result is called the Philadelphia chromosome, named after the city where researchers discovered it. More than 90% to 95% of people with CML have this distinctive genetic abnormality.^[7][5]

The BCR-ABL gene produces an abnormal protein that acts like a broken switch. Normally, tyrosine kinase enzymes in cells help control cell growth by turning on and off. However, the abnormal tyrosine kinase produced in CML doesn’t have an “off” switch. Without this control mechanism, myeloid stem cells in the bone marrow divide and multiply uncontrollably. Over time, these abnormal cells make unusually large amounts of immature white blood cells called blasts.^[2]

Eventually, the blasts accumulate in the bone marrow, crowding out the space needed to produce normal red blood cells, white blood cells, and platelets. This leads to the various health problems associated with CML. It’s important to understand that the Philadelphia chromosome is not passed from parent to child. It develops during a person’s lifetime, and the exact trigger for why this happens remains unknown in most cases.^[5]

Risk Factors

Unlike many other cancers, chronic myeloid leukaemia has very few known risk factors. The only clearly established risk factor is exposure to high levels of radiation. This was demonstrated by increased rates of CML among survivors of atomic bombs, who were exposed to intense radiation. However, this applies to very few people in the general population.^[7][2]

Age is another factor that affects CML risk. The likelihood of developing this condition increases as people get older, with most cases occurring in adults during or after middle age. Men have a slightly higher risk than women, though the difference is not dramatic.^[2]

Importantly, CML is not caused by lifestyle factors such as diet, smoking, or lack of exercise. It is not contagious and cannot be spread from person to person. There is no evidence that family history plays a significant role in most cases, as the genetic mutation occurs randomly during a person’s life rather than being inherited. The majority of people who develop CML have no identifiable risk factors, making it difficult to predict who will develop the disease.^[2]

Symptoms

One of the most challenging aspects of chronic myeloid leukaemia is that many people have no noticeable symptoms at all when they are first diagnosed. The disease often progresses so slowly that it may be discovered only during routine blood tests that show unusual blood cell counts. When symptoms do occur, they tend to be mild at first and gradually worsen over time.^[1][2]

The most common symptom reported by people with CML is fatigue or extreme tiredness. This happens because the disease affects the production of normal red blood cells, which carry oxygen throughout the body. Without enough healthy red blood cells, people feel weak and exhausted even after rest. Some people also experience shortness of breath, particularly during physical activities.^[2]

Weight loss without trying is another frequent symptom. People with CML may lose weight even though they haven’t changed their eating habits or increased their activity level. This unintentional weight loss often accompanies a decreased appetite or feeling full after eating only small amounts of food.^[1]

Many people with CML experience drenching night sweats that can soak through nightclothes and bedding. Some also develop unexplained fevers. These symptoms occur because the body is working hard to fight the abnormal cells. Pain or a feeling of fullness in the upper left part of the abdomen is another common complaint. This happens when the spleen becomes enlarged as it tries to filter out abnormal blood cells. In some cases, the enlarged spleen can be felt during a physical examination or may cause noticeable swelling in the belly area.^[1][2]

Other symptoms can include bone pain, bleeding more easily than usual, and blurry vision caused by bleeding in the back of the eye. However, because CML develops slowly, you may have the condition for years before noticing any of these symptoms. Many people learn they have CML only after routine blood test results show unusual cell counts during check-ups for unrelated health concerns.^[1]

Prevention

Unfortunately, there are no known ways to prevent chronic myeloid leukaemia in most cases. Because the genetic mutation that causes CML occurs randomly during a person’s lifetime and is not related to lifestyle factors, typical cancer prevention strategies such as maintaining a healthy diet, exercising regularly, or avoiding tobacco do not reduce the risk of developing CML.^[2]

The only identified risk factor for CML is exposure to high levels of radiation, but this applies to very few people. For those who work in environments where radiation exposure is possible, following proper safety protocols and wearing protective equipment can help minimize risk. However, the everyday radiation exposure from medical X-rays or other common sources is not considered a significant risk factor for CML.^[2]

While CML cannot be prevented, early detection through routine blood tests can lead to earlier treatment and better outcomes. If you have regular health check-ups that include blood work, any unusual changes in your blood cell counts can be identified quickly. This is particularly important for older adults, who are at higher risk for developing CML. If routine blood tests show abnormal results, your doctor may recommend additional testing to rule out conditions like CML.^[2]

Pathophysiology

Pathophysiology refers to the changes in normal body functions that occur when disease develops. In chronic myeloid leukaemia, the disease fundamentally alters how bone marrow produces blood cells. Understanding these changes helps explain why CML causes the symptoms and complications it does.^[5]

Normally, bone marrow produces blood stem cells that mature into three types of blood cells. Red blood cells carry oxygen throughout the body, platelets help blood clot to stop bleeding, and white blood cells fight infection. This process is carefully controlled so that the body makes just the right number of each type of cell. In CML, this orderly process breaks down completely.^[5]

The BCR-ABL gene created by the Philadelphia chromosome produces an abnormal tyrosine kinase protein. This protein disrupts several important pathways in cells that normally control cell growth, survival, and death. The affected pathways include JAK/STAT, PI3K/AKT, and RAS/MEK. When these pathways malfunction, cells receive signals to keep growing and dividing without stopping. They also don’t die when they should, as the normal process of cell death called apoptosis is blocked.^[7]

As a result, myeloid stem cells in the bone marrow multiply uncontrollably, producing massive numbers of immature white blood cells. These abnormal cells, called blasts, don’t function properly and can’t fight infections the way normal white blood cells do. As they accumulate in the bone marrow, they take up space that should be used for producing normal blood cells.^[5]

This crowding effect in the bone marrow leads to several problems. The production of normal red blood cells decreases, causing anemia, which is why people feel tired and weak. The body may produce more platelets than normal in early stages, but these don’t always work properly. The spleen tries to filter out the abnormal cells from the blood, which causes it to enlarge. An enlarged spleen, or splenomegaly, can cause pain and a feeling of fullness in the abdomen.^[2]

Without treatment, CML progresses through different phases. In the chronic phase, which is when most people are diagnosed, the disease is relatively stable. However, over time, the number of blast cells increases. If left untreated, CML can transform into more aggressive forms of leukaemia, similar to acute leukaemia. This transformation typically takes three to four years without treatment but can be prevented with proper medical care.^[2]