Chronic myeloid leukemia
Chronic myeloid leukemia is a myeloproliferative neoplasm driven by the Philadelphia chromosome t(9;22), which produces the constitutively active BCR-ABL1 tyrosine kinase and marked, left-shifted granulocytosis with a low leukocyte alkaline phosphatase score. Diagnosis is confirmed by cytogenetics or molecular testing for BCR-ABL1, and a BCR-ABL tyrosine kinase inhibitor such as imatinib is first-line, continued indefinitely with molecular-response monitoring, reserving allogeneic transplant for TKI failure or blast crisis.
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What this article covers
- Overview
Definition: chronic myeloid leukemia (CML) is a clonal myeloproliferative neoplasm of the hematopoietic stem cell, defined by the Philadelphia chromosome, a reciprocal translocation t(9;22) that…
- Epidemiology
Proportion of leukemia: CML accounts for about 20% of all leukemias.
- Risk factors
Age: the dominant demographic risk factor, with incidence increasing through middle and older age.
- Pathophysiology
Reciprocal translocation t(9;22)(q34;q11): juxtaposes the ABL1 tyrosine kinase gene from chromosome 9 next to the BCR gene on chromosome 22, creating the derivative chromosome 22 known as the Philadelphia chromosome.
- Clinical features
Asymptomatic neutrophil elevation: the most common presentation is an incidental marked leukocytosis found on routine laboratory testing, before symptoms appear.
- Differential diagnosis
Leukemoid reaction: reactive neutrophilia (often above 50,000/mm³), usually from severe infection, with mature cells and an elevated (not low) LAP score, the key discriminator from CML.
- Diagnosis
Confirm with cytogenetics or molecular testing for BCR-ABL1; this is what establishes the diagnosis, not the blood count alone: demonstration of the Philadelphia chromosome t(9;22) by conventional…
- Management
Start a BCR-ABL tyrosine kinase inhibitor at diagnosis for all patients; treatment is required in every phase, not deferred for asymptomatic disease.
- Complications
Blast crisis: transformation to a secondary acute leukemia (myeloid or lymphoid), the most feared complication and the main driver of CML mortality.
- Prognosis
Excellent on TKI therapy: 5-year overall survival exceeds 90% for chronic-phase CML treated with a BCR-ABL tyrosine kinase inhibitor, a dramatic improvement from the pre-TKI era.
- Prevention
No primary prevention exists because the Philadelphia chromosome is an acquired somatic mutation, not a modifiable or inherited risk factor; there is no established screening program for asymptomatic average-risk adults.
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