Chronic myeloid leukaemia (BCR-ABL1 positive)


This is a clonal myeloproliferative disorder characterized by an increase in neutrophils and their precursors in the peripheral blood with increased cellularity of the marrow as a result of an excess of granulocyte precursors. The leukaemic cells of patients have a reciprocal translocation between the long arms of chromosomes 9 and 22, t(9;22). The derived chromosome 22 is termed the Philadelphia (Ph) chromosome (Fig. 24.1). Molecular analysis shows a fusion gene BCR-ABL1 and its corresponding RNA. The disease may transform from a relatively stable chronic phase to an acute leukaemia phase (blast transformation).




Aetiology and pathophysiology


Aetiology is unknown. Exposure to ionizing radiation is a risk factor. The ABL1 gene is translocated from chromosome 9 into the breakpoint cluster region (BCR) on chromosome 22 to form the BCR-ABL1 fusion gene (Fig. 24.1). This fusion gene encodes a 210-kDa protein with greatly increased tyrosine kinase activity compared to the normal ABL1 product. The disease is of stem cell origin as the Ph chromosome is present in erythroid, granulocytic, megakaryocytic and T-lymphoid precursors. Rare cases show variant translocations or are Ph-negative but show the BCR-ABL1 fusion gene. The Ph chromosome abnormality may also occur in acute lymphoblastic leukaemia (ALL; see Chapter 22).



Clinical features



  • The disease occurs at all ages (peak age of 25–45 years, male : female ratio equal, incidence of 5–10 cases per million population).
  • Patients usually present in the chronic phase.
  • Presenting symptoms include weight loss, night sweats, itching, left hypochondrial pain, gout.
  • Priapism, visual disturbance and headaches caused by hyperviscosity (WBC >250 × 109/L) are less frequent.
  • Splenomegaly, often massive, occurs in over 90% of cases.
  • Some cases are discovered on a routine blood test.

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Jun 12, 2016 | Posted by in HEMATOLOGY | Comments Off on Chronic myeloid leukaemia (BCR-ABL1 positive)

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