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Chronic myeloid leukemia

Last reviewed dd mmm yyyy. Last edited dd mmm yyyy

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Chronic myeloid leukaemia is a malignant clonal proliferation of an abnormal haemopoietic stem cell. Over a period of many months the cell line expands, producing myeloid cell types. Normal haemopoiesis is gradually replaced.

Chronic myeloid leukaemia accounts for 20% of all leukaemias. It occurs mainly in middle aged and elderly people and is characterised by marked leucocytosis, a left shifted myeloid series and in 95% of patients, the Philadelphia chromosome.

  • characteristic genetic abnormality of CML, the Philadelphia (Ph) chromosome, results from a reciprocal translocation between the long arms of chromosomes 9 and 22
  • molecular consequence of this translocation is the fusion of the ABL gene (encoding a nonreceptor tyrosine kinase) with the BCR gene generating a chimeric gene BCR-ABL, which in turn is translatedto a fusion protein (Bcr-Abl), a constitutively activated tyrosine kinase, which is present in virtually all patients with CML (1,2)

CML develops insidiously. Initial symptoms are often nonspecific and due to anaemia or hypermetabolism. Weakness, weight loss and fatigue are common. Massive splenomegaly is characteristic and may cause left hypochondral pain.

The condition usually remains stable for years and then transforms to a more overtly malignant disease. It is invariably fatal but patients may enjoy a near normal life during the chronic phase.

Allogeneic bone marrow transplantation, the only curative treatment for CML, is associated with substantial morbidity and mortality and is limited to patients for whom a suitable donor is available.

Note:

  • some patients with features of CML will not present with Philadelphia chromosome or BCR-ABL rearrangement. They are considered to represent a separate disease entity and are referred to as Philadelphia negative and BCR-ABL negative, or atypical CML (3).

Reference:


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