Chronic myeloid leukaemia
- Lesion
One swapped chromosome makes a kinase that never switches off. The blood fills with granulocytes, the spleen swells, and tablets now control it.
What it is
Chronic myeloid leukaemia (CML) arises in a pluripotent stem cell carrying the Philadelphia chromosome, t(9;22), which creates the BCR::ABL1 fusion tyrosine kinase. The kinase drives growth-factor-independent proliferation, mostly of granulocytic and megakaryocytic progenitors, with release of immature forms. Untreated, a chronic phase lasting a few years gives way to an accelerated phase and blast crisis, which can be myeloid or lymphoid because the disease starts in a stem cell. Kinase inhibitors have transformed the outlook.
Structure
- Marrow: close to 100% cellular, mostly maturing granulocytes; megakaryocytes increased, often small; scattered sea-blue histiocytes.
- Spleen: red pulp full of granulocytic precursors, resembling marrow; infarcts are common.
- Blood smear: the whole granulocytic maturation sequence plus basophils.
Step by step
- A stem cell acquires t(9;22), forming BCR::ABL1.
- The fusion kinase activates RAS–MAPK, PI3K–AKT and STAT pathways without growth factors.
- Granulocytic and megakaryocytic output rises; immature cells leave the marrow early.
- Extramedullary haematopoiesis enlarges spleen and liver.
- Additional mutations block differentiation: accelerated phase, then blast crisis.
CML vs leukaemoid reaction
| Feature | Chronic myeloid leukaemia | Leukaemoid reaction |
|---|---|---|
| Basophils and eosinophils / BCR::ABL1 | Increased basophils and eosinophils; BCR::ABL1 present | Not increased; BCR::ABL1 absent |
| Cause and course | Clonal stem cell neoplasm; progressive | Severe infection or tumour; resolves with the cause |
Markers
- BCR::ABL1 by PCR or FISH
- Philadelphia chromosome on karyotype
Clinical notes
- Fatigue, weight loss, left upper quadrant dragging from a big spleen in a middle-aged adult.
- Daily oral BCR::ABL1 kinase inhibitors give long survival; resistance comes from kinase mutations, handled with later-generation inhibitors.
- Molecular monitoring of BCR::ABL1 transcripts tracks response; some patients in deep remission can stop treatment.
Test yourself
Think of the answer, then tap the question to see it.
Why can CML blast crisis be lymphoid?
The disease starts in a pluripotent stem cell that can give rise to both myeloid and lymphoid cells.
Which blood finding helps separate CML from a leukaemoid reaction?
Basophilia (and eosinophilia), together with the BCR::ABL1 fusion.
Which phase follows untreated chronic phase CML?
An accelerated phase and then blast crisis, an acute leukaemia.
Elsewhere in DurgiPedia
Connections
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Chronic Myeloid Leukemia Treatment (PDQ®)–Patient Version (National Cancer Institute (NCI), 2026); Chronic myeloid leukemia: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026).
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Representative model, for educational purposes only.