Chronic myeloid leukemia (CML) is a slow-growing blood cancer caused by an acquired genetic change, the Philadelphia chromosome, in a bone marrow stem cell. Many people have no symptoms and are diagnosed after a routine blood test shows a very high white cell count. When symptoms appear, fatigue, night sweats, weight loss, and a full or aching feeling under the left ribs from an enlarged spleen are the most common. Daily tablets called tyrosine kinase inhibitors (TKIs) have transformed treatment, and most people diagnosed in the chronic phase now have a near-normal life expectancy.
What Is Chronic Myeloid Leukemia?
CML starts in a blood-forming stem cell in the bone marrow. The abnormal stem cell and its descendants overproduce myeloid cells, especially granulocytes such as neutrophils. Unlike acute leukemia, the cells in early CML still mature, so the blood fills with large numbers of fairly normal-looking white cells.
CML is mainly a disease of adults, most often diagnosed in middle age or later, and it is rare in children. It is not contagious and is not passed from parent to child.
The Three Phases of CML
| Phase | What happens | Typical features |
|---|---|---|
| Chronic phase | Stable, slow growth; most patients are diagnosed here | High white count, few blasts, often mild or no symptoms |
| Accelerated phase | Disease becomes less stable | Rising blasts or basophils, falling or very high platelets, new genetic changes, growing spleen |
| Blast phase (blast crisis) | Behaves like acute leukemia | Blasts of 20% or more in blood or marrow, marked anemia, bleeding, infections |
Newer classification systems place less emphasis on a separate accelerated phase, focusing instead on high-risk features. The practical message is the same: treating CML well in the chronic phase keeps it from progressing.
Causes and Risk Factors
CML is caused by a swap of genetic material between chromosomes 9 and 22, called a translocation. The shortened chromosome 22 is known as the Philadelphia chromosome. It joins two genes, BCR and ABL1, into a single fusion gene.
The BCR-ABL1 fusion gene produces an enzyme, a tyrosine kinase, that is permanently switched on. It sends constant “grow and survive” signals to the cell, so myeloid cells multiply without the usual brakes and resist normal cell death.
This genetic change is acquired during life, not inherited. In most people, no cause is ever found. The only well-established risk factor is exposure to high doses of ionizing radiation. Diet, lifestyle, and family history do not appear to play a meaningful role.
Symptoms of CML
Symptoms depend on the phase and on how high the blood counts are. Common ones include:
- Tiredness and low energy, from anemia.
- Night sweats and unexplained weight loss.
- Fullness, discomfort, or feeling full after small meals, from an enlarged spleen (splenomegaly).
- Bone pain.
- Easy bruising or bleeding.
- Fever and repeated infections, particularly in advanced phases.
Rarely, an extremely high white count thickens the blood and causes headaches, visual changes, or breathlessness. This is called leukostasis and needs urgent treatment.
How CML Is Diagnosed
In my practice, CML is often suspected from the complete blood count (CBC) alone. A very high white cell count with myeloid cells at every stage of maturity, plus raised basophils, is highly suggestive. Diagnosis is then confirmed with:
- Bone marrow aspirate and biopsy: shows how crowded the marrow is, counts blasts to determine the phase, and allows chromosome analysis.
- Cytogenetics and FISH: detect the Philadelphia chromosome and any additional chromosome changes.
- Quantitative PCR for BCR-ABL1: measures the amount of fusion gene in the blood. This becomes the main monitoring test.
For a closer look at the workup, including how phase and risk are assigned, see our leukemia guide.
Treatment Approaches
TKIs block the overactive BCR-ABL1 enzyme directly. They are taken as tablets, usually once or twice daily, and are the standard first treatment for chronic-phase CML.
| Treatment | Role |
|---|---|
| Imatinib | First TKI; still widely used first-line |
| Dasatinib, nilotinib, bosutinib | Second-generation TKIs; first-line or after intolerance or resistance |
| Ponatinib | For resistant disease, including the T315I mutation |
| Asciminib | Targets a different site on the BCR-ABL1 enzyme; used for resistant or intolerant disease |
| Stem cell transplant | For blast phase or disease that fails several TKIs |
The choice of TKI depends on the patient’s other health conditions and side-effect profile. Common side effects include tiredness, muscle cramps, rash, fluid retention, and upset stomach. Some TKIs carry specific risks, such as fluid around the lungs or effects on the heart and blood vessels, which guide selection.
Monitoring and Treatment-Free Remission
Response is tracked with BCR-ABL1 PCR, usually every three months at first. A level of 0.1% or less on the international scale is called a major molecular response, and it signals a very low risk of progression.
Some patients who achieve a deep, sustained molecular response for several years can stop their TKI under close monitoring. This is called treatment-free remission. A substantial share stay in remission off treatment; those who relapse almost always respond again when the TKI is restarted.
Living Well With CML on a TKI
Most people on a TKI work, travel, and exercise as usual. The single most important habit is taking the tablet every day as prescribed, because missed doses are a leading cause of losing response.
Some TKIs must be taken on an empty stomach, and several interact with other medicines, grapefruit, and certain herbal products. Always tell your pharmacist and other doctors that you take a TKI. Anyone planning a pregnancy should discuss it with their hematologist well in advance, as TKIs are generally avoided during pregnancy.
Key Takeaways
- CML is caused by the acquired Philadelphia chromosome and its BCR-ABL1 fusion gene.
- Many patients have no symptoms; others notice fatigue, night sweats, weight loss, or an enlarged spleen.
- Diagnosis rests on the blood count, bone marrow testing, and genetic tests for BCR-ABL1.
- TKI tablets are the mainstay of treatment and give most chronic-phase patients a near-normal outlook.
- Taking the TKI consistently and attending regular PCR monitoring are the keys to long-term control.
Frequently Asked Questions
Is CML curable?
Transplant can cure CML but is reserved for advanced or resistant cases because of its risks. For most people, TKIs control the disease so well that it behaves like a long-term condition, and some can eventually stop treatment.
Will I need to take TKI tablets for life?
Many people take them indefinitely. Those who reach a deep, stable response for several years may be able to try stopping under specialist supervision, with close PCR monitoring afterward.
Can CML turn into acute leukemia?
Without effective treatment, CML eventually progresses to blast phase, which behaves like acute leukemia. With modern TKIs and good adherence, progression has become uncommon.
Is CML hereditary?
No. The Philadelphia chromosome develops in a single bone marrow cell during a person’s life. It is not present in eggs or sperm and cannot be passed to children.
