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Chronic myeloid leukemia

Last updated: May 27, 2021

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Chronic myeloid leukemia (CML) belongs to the group of myeloproliferative neoplasms. It is a malignancy of the hematopoietic stem cells with excessive proliferation of the myeloid lineage (especially granulocytes). It is caused by a cytogenetic aberration (Philadelphia chromosome 22) that results in the formation of a BCR-ABL fusion gene. The increased activity of this gene's product – a tyrosine kinase – promotes unregulated proliferation of myeloid progenitor cells, which eventually differentiate into mature cells. CML has three distinct clinical phases. The chronic phase is characterized by nonspecific symptoms (fever, weight loss, night sweats) and splenomegaly and can persist for up to 10 years. The accelerated phase is characterized by complications secondary to the suppression of the other cell lines (thrombocytopenia, anemia, recurrent infections). The clinical picture of the terminal phase, blast crisis, resembles that of acute leukemia. Important diagnostic features are severe leukocytosis (> 500,000/μl), basophilia, and extreme splenomegaly. The most important therapeutic principle is targeted therapy with imatinib, which selectively inhibits BCR-ABL tyrosine kinase. This drug has revolutionized CML treatment and greatly improved the prognosis of CML.


Epidemiological data refers to the US, unless otherwise specified.


Philadelphia chromosome

Malignancy Detection of Philadelphia translocation
  • > 90% of patients
  • ∼ 20% of adults
  • ∼ 5% of children
  • < 2% of patients

Genetic changes and clinical course


Chronic phase

Unlike AML, CML is not characterized by recurrent infections during early stages, since the granulocytes are still fully functional.

Accelerated phase

Blast crisis

The blast crisis is the terminal stage of CML.


Peripheral blood analysis

CML causes the most severe leukocytosis (> 500,000/μl) of all forms of leukemia. Increasing basophilia is a sign of acceleration.

Low LAP is a distinct feature of CML that distinguishes it from all other forms of leukemia!

Bone marrow

WHO classification of the CML phases

CML Phase Blast count in peripheral blood and bone marrow
Chronic < 10%
Accelerated 10–19%
Blast Crisis ≥ 20%



Differential diagnosis between leukemoid reaction and myeloproliferative neoplasms
Disease CBC and peripheral blood smear LAP score Genetics/cause
Polycythemia vera
  • JAK2 mutation in 95% of cases
Primary myelofibrosis
  • JAK2 mutation in up to 60% of cases
Essential thrombocythemia
  • JAK2 mutation in 50% of cases
Chronic myeloid leukemia
Leukemoid reaction [9]
  • No mutation
  • Typically secondary to infections or drugs (e.g., steroids)
  • Associated with certain solid tumors (e.g., lung and kidney cancer)

The differential diagnoses listed here are not exhaustive.

  • Survival rate without treatment:
    • Chronic phase: 3.5–5 years
    • Blast phase: 3–6 months
  • In most patients, life expectancy can be markedly improved through targeted therapy with imatinib. In some cases, it even results in molecular remission.


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