Chronic Myeloid Leukaemia

Chronic Myeloid Leukaemia is a tri-phasic myeloproliferative disorder. Patients usually present in chronic phase, characterised by granulocytosis and thrombocytosis. Splenomegaly is common. Without effective treatment, the disease progresses to an accelerated phase characterised by increasing white cell count, clonal evolution and rising blast count, culminating in a terminal blastic phase morphologically indistinguishable from acute leukaemia. Formation of the BCR-ABL1 fusion oncogene through translocation of chromosomes 9 and 22 is the underlying genetic lesion, encoding a constitutively active tyrosine kinase. This leads to growth disinhibition, and reduced apoptosis. Treatment with tyrosine kinase inhibitors (TKI) is highly effective in chronic phase and leads to excellent long term survival, though treatment responses in blastic phase disease with TKI monotherapy is usually transient.