Chronic myeloid leukemia (CML) is a slow-growing blood cancer caused by a single genetic change, the BCR-ABL1 fusion gene, which drives the bone marrow to overproduce white blood cells. Treating it means switching off that gene’s protein with a daily pill called a tyrosine kinase inhibitor (TKI). With this approach, most people diagnosed in the chronic phase now live a near-normal lifespan. Below I review how CML develops, how it is diagnosed and monitored, and how treatment is chosen.
What Is Chronic Myeloid Leukemia?
CML is a cancer of the myeloid cells, the family that includes neutrophils, basophils, and the precursors of red blood cells and platelets. It starts in a single stem cell in the bone marrow, whose descendants gradually crowd the blood with excess white cells.
It differs from acute leukemias because the cells still mature, so the disease often progresses slowly over years. It also differs from lymphoid cancers, such as the one described in our article on B-cell acute lymphoblastic leukemia. CML sits within the wider field of hematology and is one of the best-understood cancers at the molecular level.
Causes: The Philadelphia Chromosome
Almost every case of CML carries the Philadelphia chromosome, a shortened chromosome 22 created when pieces of chromosomes 9 and 22 swap places, written as t(9;22). This swap fuses two genes, BCR and ABL1. The resulting protein is a tyrosine kinase that is permanently switched on, signaling cells to divide and resist normal cell death.
The change is acquired, not inherited. It arises by chance in a single cell during a person’s lifetime, so CML does not run in families and cannot be passed to children. The only well-established risk factor is exposure to high doses of ionizing radiation. CML is most often diagnosed in middle-aged and older adults, although it can occur at any age, including in children.
Symptoms and the Three Phases
Many people have no symptoms, and CML is often found on a routine blood count showing a high white cell count. When symptoms occur, they include fatigue, weight loss, night sweats, and a feeling of fullness or discomfort under the left ribs from an enlarged spleen.
| Phase | Features | Outlook with treatment |
|---|---|---|
| Chronic phase | High white count, few immature blast cells, mild or no symptoms | Most patients are diagnosed here and respond well to TKIs |
| Accelerated phase | Rising blasts or basophils, falling platelets, new genetic changes | Harder to control; treatment is intensified |
| Blast phase | Many blasts; behaves like an acute leukemia | Serious; requires intensive treatment and often a transplant |
Some newer classifications no longer separate an accelerated phase and instead focus on high-risk features. The practical message is the same: the aim of treatment is to keep the disease in the chronic phase.
How CML Is Diagnosed
Diagnosis usually follows three steps:
- Complete blood count and blood smear: typically a raised white count with cells at every stage of maturity, often with more basophils and sometimes a high platelet count.
- Bone marrow aspirate and biopsy: shows how crowded the marrow is and counts blasts to establish the phase. Cytogenetic analysis identifies the Philadelphia chromosome and any extra changes.
- Molecular testing: quantitative polymerase chain reaction (qPCR) detects the BCR-ABL1 transcript and measures how much is present. This becomes the baseline for monitoring.
Treating Chronic Myeloid Leukemia
For a wider view of the options, see our guide to myeloid leukemia treatment. In CML, treatment is built around TKIs.
Tyrosine Kinase Inhibitors
| Drug | Generation | Side effects to watch for |
|---|---|---|
| Imatinib | First | Fluid retention, muscle cramps, nausea, rash |
| Dasatinib | Second | Fluid around the lungs (pleural effusion), low blood counts |
| Nilotinib | Second | Heart rhythm (QT) changes, raised blood sugar and cholesterol, artery problems |
| Bosutinib | Second | Diarrhea, liver enzyme changes |
| Ponatinib | Third | Blood clots and artery disease; active against the T315I mutation |
| Asciminib | Allosteric (STAMP) inhibitor | Generally well tolerated; used after other TKIs or for T315I |
The first choice depends on disease risk, other health conditions, and side-effect profiles. Taking the tablet every day matters a great deal. Missed doses are a common reason for losing response.
Monitoring the Response
BCR-ABL1 levels are checked by qPCR, usually every three months at first, and reported on the International Scale (IS). Widely used milestones aim for 10% or less at 3 months, 1% or less by 6 months, and 0.1% or less, called major molecular response, by 12 months. Missing a milestone prompts a check on adherence, testing for resistance mutations, and often a switch of TKI.
When a TKI Is Not Enough
For resistance to several TKIs or progression to advanced phase, allogeneic stem cell transplantation remains the only established cure. It carries significant risks, so it is reserved for selected patients. Our overview of leukemia from diagnosis to advanced treatment explains how transplant fits in.
Living Well on Long-Term Treatment
Because TKIs are often taken for years, managing side effects is part of good care. Many early effects, such as nausea or cramps, settle within the first months, and dose adjustments or a change of drug can help when they do not.
Some TKIs interact with other medicines, grapefruit, or certain supplements, and nilotinib must be taken on an empty stomach. Keep an updated medication list, tell every prescriber you are on a TKI, and keep up routine checks of blood pressure, blood sugar, and cholesterol.
Stopping Treatment: Treatment-Free Remission
Some patients who achieve a deep, sustained molecular response over several years may be able to stop their TKI under close supervision. This is called treatment-free remission. A proportion stay in remission off treatment. Those who relapse usually regain their response when the TKI is restarted, which is why monthly PCR monitoring is essential in the first months after stopping.
Key Takeaways
- CML is driven by the BCR-ABL1 fusion gene created by the Philadelphia chromosome.
- Most patients are diagnosed in the chronic phase, often from a routine blood test.
- Daily TKI therapy controls the disease in most people and allows a near-normal life expectancy.
- Regular qPCR monitoring guides treatment, and some patients can eventually stop treatment safely.
Frequently Asked Questions
Is chronic myeloid leukemia curable?
Stem cell transplant can cure CML, but most patients do not need it. TKIs control the disease long-term, and some people reach treatment-free remission, which functions much like a cure while monitoring continues.
How long do people live with CML?
For most people diagnosed in the chronic phase who respond to TKIs and take them consistently, life expectancy approaches that of the general population. Outcomes are less favorable in advanced phases.
Do I have to take TKI medication forever?
Many people take it long-term. Those with a deep, stable response for several years may be offered a supervised trial off treatment.
Can I have children while being treated for CML?
TKIs can harm a developing baby, so pregnancy needs careful planning with your hematologist. Treatment may be paused or adjusted under close monitoring, and men should also discuss their plans with the care team.
