Molecular evolution of chronic myeloid leukaemia

Chronic myeloid leukaemia (CML) is a clonal disorder of the pluripotent haematopoietic stem cell. The typical triphasic course of CML starts with the premalignant chronic phase initiated by BCR-ABL hybrid oncogene formation. Secondary genetic and epigenetic aberrations accompany the progression to the accelerated phase and fatal blastic crisis. Properly timed bone marrow transplantation in eligible patients can result in durable remissions or cure. Both of these states are often accompanied by a long-term persistence of quiescent leukaemic cells. Accordingly, a 'functional cure' (i.e. tumour dormancy induction), rather than complete eradication of the malignant cells, is an adequate therapeutical goal. The level of the residual BCR-ABL-positive clones should be monitored and salvage treatment initiated whenever these quiescent leukaemic cells exit their dormant state.