Chronic myeloid leukaemia

Chronic myeloid leukaemia

The Philadelphia chromosome

Philadelphia chromosome

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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)

translocation between the long arm of chromosome 9 and 22 - t(9:22)(q34; q11)

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. 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
  splenomegaly
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  may be marked → abdo discomfort
• an increase in granulocytes at different stages of maturation +/- thrombocytosis
  In chronic myeloid leukaemia there is an increase in granulocytes at different stages of maturation +/- thrombocytosis
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  Importance: 69
• 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
    Chronic myeloid leukaemia - imatinib = tyrosine kinase inhibitor
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    Importance: 52
    associated with the BCR-ABL defect
  • very high response rate in chronic phase CML
• hydroxyurea
• interferon-alpha
• allogenic bone marrow transplant

+PassMedicine Notes

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