Conditions · Hematology and oncology
Chronic myeloid leukaemia !
Chronic myeloid leukaemia is a bone-marrow cancer driven by the Philadelphia chromosome; targeted tablets now control it for many years.
Updated 2026-11-01
Structures involved
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Why it happens
- Molecular pathology: PCR, FISH, sequencing and liquid biopsy
- Oncogenes: RAS, MYC, HER2, BCR-ABL and the table to know
- Translocations, amplifications and epigenetic changes in cancer
- The hallmarks of cancer
- Chromosome abnormalities: number and structure
- Radiation and cancer: ultraviolet and ionizing
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What it is
A myeloproliferative neoplasm in which a haematopoietic stem cell carrying the BCR-ABL1 fusion gene produces too many granulocytes at all stages of maturation. It runs a chronic phase that, without treatment, progresses to an accelerated phase and a blast crisis.
Who gets it
Accounts for about 15% of adult leukaemias and is most often diagnosed in middle age, slightly more in men. Many cases are found by chance on a blood count. In Colombia it is managed in specialised haematology centres, and access to targeted therapy and molecular monitoring determines outcomes.
Causes
- Reciprocal translocation t(9;22) forming the Philadelphia chromosome
- BCR-ABL1 fusion gene encoding a constantly active tyrosine kinase
- High-dose ionising radiation exposure in a minority; most cases have no known cause
Risk factors
- Middle or older age
- Male sex
- Prior exposure to high doses of radiation
Pathophysiology
The BCR-ABL1 tyrosine kinase continuously signals for proliferation and blocks apoptosis, so the marrow fills with myeloid cells that spill into the blood and colonise the spleen. Cells still mature, which keeps the chronic phase relatively stable. Over time additional mutations block maturation, blasts accumulate and the disease behaves like an acute leukaemia (blast crisis, myeloid or lymphoid).
Classification
- Chronic phase: blasts below 10% in blood or marrow (most patients at diagnosis)
- Accelerated phase: blasts 10–19%, rising counts or new cytogenetic changes
- Blast phase (blast crisis): blasts 20% or more, or extramedullary blast infiltration
Symptoms and signs
- Often no symptoms; found on a routine blood count
- Fatigue, weight loss and night sweats
- Left upper quadrant fullness, early satiety or pain from an enlarged spleen
- Bone pain, sternal tenderness
- Bruising or bleeding; infections and fever in advanced phases
Diagnosis
- Clinical
- Marked splenomegaly on examination in a patient with leukocytosis is the classic finding.
- Tests
- Very high white count with granulocytes at all stages of maturation, basophilia and eosinophilia, often thrombocytosis. Hypercellular bone marrow. The Philadelphia chromosome by karyotype or FISH and BCR-ABL1 transcripts by quantitative PCR confirm the diagnosis and are used to monitor response. Low leukocyte alkaline phosphatase helps separate it from a leukaemoid reaction.
- Imaging
- Ultrasound measures spleen size; not needed for diagnosis.
Differential diagnosis
- Leukaemoid reaction from infection or inflammation
- Other myeloproliferative neoplasms (polycythaemia vera, essential thrombocythaemia, primary myelofibrosis)
- Chronic myelomonocytic leukaemia
- Acute leukaemia (when blasts are high)
Goal of treatment
Suppress the BCR-ABL1 clone to deep molecular response, prevent progression to blast crisis and preserve quality of life; in selected patients with sustained deep response, treatment-free remission can be attempted.
Treatment
- Medical
- Tyrosine kinase inhibitors that block BCR-ABL1 (imatinib as the first in class; second- and third-generation agents for resistance or intolerance) are first-line therapy for chronic phase.
- Medical
- Cytoreduction with hydroxyurea for very high counts while the diagnosis is confirmed; leukapheresis for leukostasis.
- Follow-up
- Regular blood counts and quantitative BCR-ABL1 PCR to measure molecular response, check adherence and detect resistance mutations.
- Procedure
- Allogeneic stem cell transplant for blast crisis or disease resistant to several inhibitors.
Complications
- Progression to accelerated phase or blast crisis
- Leukostasis and thrombosis with very high counts
- Splenic infarction or rupture
- Hyperuricaemia, gout and tumour lysis syndrome during cytoreduction
- Drug side effects such as fluid retention, cytopenias and cardiovascular events
Prognosis
Tyrosine kinase inhibitors transformed CML: most patients in chronic phase who adhere to treatment have a life expectancy close to that of the general population. Blast crisis remains hard to treat.
Test yourself
Think of the answer, then tap the question to see it.
Which cytogenetic abnormality defines chronic myeloid leukaemia?
The Philadelphia chromosome, t(9;22), creating the BCR-ABL1 fusion gene.
What drug class is first-line treatment for chronic-phase CML?
BCR-ABL1 tyrosine kinase inhibitors, such as imatinib.
What is the classic physical finding in CML?
Marked splenomegaly.
Which laboratory finding helps distinguish CML from a leukaemoid reaction?
Low leukocyte alkaline phosphatase score plus basophilia and the BCR-ABL1 fusion in CML.
Related conditions
Educational information, not medical advice. For any symptom, see a health professional.
Sources: Chronic Myeloid Leukemia Treatment (PDQ®)–Patient Version (National Cancer Institute, 2024); Chronic myelogenous leukemia (CML) (MedlinePlus (U.S. National Library of Medicine), 2024).
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