Chronic myeloid leukemia, commonly called CML, is a type of blood cancer that begins in the blood-forming cells of the bone marrow. It is also known as chronic myelogenous leukemia. CML primarily affects adults and is characterized by the uncontrolled production of abnormal myeloid cells. Unlike acute forms of leukemia, CML generally develops more slowly. Many people have few or no noticeable symptoms when the disease is first identified. In some cases, an unusual result on a routine blood test leads to further testing and eventual diagnosis.
CML develops in the bone marrow, the soft tissue responsible for producing blood cells. The disease affects early myeloid cells, which normally develop into several types of blood cells.
A defining feature of CML is an acquired genetic change involving chromosomes 9 and 22. This rearrangement creates what is known as the Philadelphia chromosome and produces an abnormal fusion gene called BCR::ABL1.
The BCR::ABL1 gene produces an abnormal protein called a tyrosine kinase. This protein continuously sends signals that encourage abnormal blood cells to grow and multiply.
As these cells accumulate in the bone marrow and bloodstream, they can interfere with normal blood-cell production. This can eventually contribute to anemia, bleeding problems, infections, fatigue, and enlargement of the spleen.
The genetic change associated with CML generally develops during a person's lifetime rather than being inherited from a parent. Family history is therefore not considered a typical cause of CML.
Normal bone marrow produces carefully regulated numbers of red blood cells, white blood cells, and platelets. Each type has a specific role in maintaining the body's functions.
In CML, the BCR::ABL1 fusion gene alters the signaling mechanisms controlling cell growth. Abnormal myeloid cells continue multiplying when normal regulatory mechanisms would normally slow or stop that growth.
Large numbers of abnormal white blood cells can then enter the bloodstream. As the disease progresses, the growing population of leukemia cells can affect the production of healthy blood cells.
The Philadelphia chromosome is present in most cases of CML. Laboratory testing for BCR::ABL1 is therefore an important part of confirming the diagnosis.
CML can remain unnoticed for a considerable period. Some people have no symptoms when the disease is detected.
When symptoms occur, they may develop gradually. Common symptoms can include:
Many of these symptoms can occur with other medical conditions, so they do not automatically indicate leukemia.
An enlarged spleen can produce a feeling of pressure or fullness in the upper-left portion of the abdomen. In some people, this may be one of the first physical findings associated with CML.
The precise event that triggers the chromosome change leading to CML is not fully understood.
The disease is associated with an acquired genetic alteration that creates the BCR::ABL1 fusion gene. This change occurs after birth and is generally not passed from parents to children.
Exposure to high levels of ionizing radiation has been associated with an increased risk of CML, although this accounts for only a small proportion of cases.
For most people diagnosed with CML, there is no clear explanation for why the genetic change occurred.
CML can occur at any age, but it is much more common among adults, particularly older adults. It is uncommon in children.
Men are affected slightly more often than women.
High-dose radiation exposure is another recognized risk factor. However, most people with CML do not have a clearly identifiable cause.
Because the genetic change is usually acquired rather than inherited, having a relative with CML does not generally mean that another family member will develop the disease.
Diagnosis commonly begins with a blood test. A complete blood count may show an unusually high white blood cell count or other abnormalities.
Further testing can establish whether CML is responsible for the abnormal blood-cell pattern.
A complete blood count measures different types of blood cells. In CML, the test may show a markedly elevated white blood cell count.
Changes in red blood cells and platelets can also occur as the disease progresses.
A blood smear allows laboratory specialists to examine blood cells under a microscope. Different stages of white blood-cell development may be visible in a sample from someone with CML.
A bone marrow aspiration or biopsy can provide additional information about the number and characteristics of abnormal cells.
Bone marrow samples can also be used for chromosome and molecular testing.
Testing for the Philadelphia chromosome and BCR::ABL1 is particularly important in CML.
Several laboratory techniques can identify the abnormal genetic material. Molecular testing can also measure BCR::ABL1 levels during treatment, making it useful for monitoring the response to therapy.
CML is generally divided into three phases based on the proportion of immature leukemia cells, known as blasts, in the blood and bone marrow.
The chronic phase is the most common phase at diagnosis. It is characterized by a relatively low percentage of blast cells.
Many people diagnosed during this phase have few symptoms or no symptoms. Modern targeted treatments can control the disease effectively in many cases.
The accelerated phase represents a progression in disease activity. Blood and bone marrow contain a higher proportion of blast cells than in the chronic phase.
Changes in blood counts, increasing spleen size, worsening symptoms, or reduced response to treatment may occur.
The blastic phase is the most advanced phase of CML. Blast cells account for a much larger proportion of the blood or bone marrow and can behave similarly to cells seen in acute leukemia.
This phase is more difficult to treat and generally requires more intensive medical management.
Understanding the disease phase helps the medical team determine the appropriate treatment strategy.
Treatment depends on the disease phase, genetic findings, previous treatment, overall health, response to therapy, and other individual factors.
Tyrosine kinase inhibitors, commonly called TKIs, are the primary treatment for many people with CML.
These medicines target the abnormal BCR::ABL1 signaling pathway. By inhibiting the activity of the abnormal tyrosine kinase protein, TKIs can reduce the growth and survival of leukemia cells.
Several TKIs are used in CML treatment, including imatinib, dasatinib, nilotinib, bosutinib, and ponatinib in particular clinical circumstances.
Selection of a TKI depends on factors such as disease phase, previous therapy, treatment response, side-effect considerations, and specific genetic findings.
Regular monitoring is an important part of CML care.
Blood counts can show how the bone marrow and blood are responding. Molecular testing for BCR::ABL1 provides a more specific measurement of the leukemia burden.
Treatment response is evaluated over time rather than through a single laboratory result. A sustained molecular response can indicate strong disease control.
If response is inadequate or the disease begins progressing, the treatment plan may be reassessed.
Allogeneic stem cell transplantation can provide a potentially curative treatment for CML, but it is not routinely used as the first treatment for most people diagnosed in the chronic phase.
Transplantation may be considered in situations such as advanced disease, treatment resistance, or certain cases in which targeted medicines do not provide adequate control.
Because transplantation can involve serious complications, the potential benefits and risks require careful assessment.
Chemotherapy may have a role in advanced CML or specific treatment situations. Additional therapies may be considered depending on disease phase and previous treatment.
In certain circumstances, donor lymphocyte infusion may be used after stem cell transplantation.
Treatment plans can change over time as the disease responds or develops resistance.
Some CML cells can develop genetic changes that reduce sensitivity to a particular TKI.
When treatment response is not sufficient, clinicians may evaluate medication adherence, drug interactions, molecular response, and possible mutations in the BCR::ABL1 gene.
A change to another TKI may be considered when resistance or significant treatment-related problems occur.
The discovery of specific mutations can help inform subsequent treatment decisions.
CML can affect normal blood-cell production and other organs.
Potential complications include:
Some complications are associated with the leukemia itself, while others can result from treatment.
Monitoring blood counts, molecular markers, symptoms, and physical findings helps the medical team identify changes early.
For many people, CML becomes a long-term condition that requires regular medical follow-up.
Treatment may continue for an extended period, with periodic blood and molecular testing used to assess disease control.
Medication adherence is particularly important with oral targeted therapies. Missing doses or stopping treatment without medical supervision can affect disease control and may contribute to treatment resistance.
Side effects can vary according to the specific medication. Possible effects include fatigue, gastrointestinal symptoms, muscle cramps, fluid retention, skin changes, changes in blood counts, and other medication-specific reactions.
Any persistent or concerning side effects should be discussed with the treating medical team rather than leading to unsupervised treatment changes.
The outlook for CML has changed considerably with the development of targeted therapy.
Many people diagnosed in the chronic phase can achieve substantial and sustained control of the disease with appropriate treatment. Long-term outcomes depend on factors including disease phase, molecular response, treatment response, resistance, and general health.
A diagnosis of CML does not necessarily mean that the disease will rapidly progress. The chronic phase often develops slowly, and modern treatments can substantially reduce the activity of the leukemia.
Regular monitoring remains important because changes in molecular response can provide an early indication that treatment may need reassessment.
There is no established lifestyle strategy that can reliably prevent CML.
Because the genetic change responsible for the disease is usually acquired during a person's lifetime and the cause is often unknown, prevention is difficult.
High-dose radiation exposure is associated with increased risk, but such exposure accounts for a small number of cases.