Chronic myeloid leukaemia

The Philadelphia chromosome is present in more than 95% of patients with chronic myeloid leukaemia (CML). It is due to a translocation between the long arm of chromosome 9 and 22 - t(9:22)(q34; q11). This results in part of the ABL proto-oncogene from chromosome 9 being fused with the BCR gene from chromosome 22. The resulting BCR-ABL gene codes for a fusion protein that has tyrosine kinase activity in excess of normal.

Presentation (60-70 years)

• anaemia: lethargy
• weight loss and sweating are common
• splenomegaly may be marked → abdo discomfort
• an increase in granulocytes at different stages of maturation +/- thrombocytosis
• decreased leukocyte alkaline phosphatase
• may undergo blast transformation (AML in 80%, ALL in 20%)

Management

• imatinib is now considered first-line treatment
  • inhibitor of the tyrosine kinase associated with the BCR-ABL defect
  • very high response rate in chronic phase CML
• hydroxyurea
• interferon-alpha
• allogenic bone marrow transplant

Chronic Myeloid Leukemia (CML)

• presents with tiredness, wt. loss and sweating; if WBC is very high (>500) hyperleucocytosis -> visual disturbance, priapism, deafness, confusion; sometimes Gout
• splenomegaly in 90% of cases
• absolute basophilia and eosinophilia
• massive neutrophilia with left shift
• low neutrophil alkaline phosphatase (NAP) score