Leukaemias into the 21st century: part 1: the acute leukaemias

The leukaemias are a biologically and clinically heterogeneous group of malignancies, which manifest as clonal expansions of a single cell at different stages of lympho-haemopoietic development. The transformed cell acquires an unrestrained capacity for self-renewal and, in the case of the acute leukaemias, also fails to differentiate into functional mature cells. Historically leukaemias were classified using a combination of clinical and (presumed) cell lineage criteria. Thus, the four major subgroups of acute and chronic myeloid leukaemia and acute and chronic lymphoid leukaemia were recognised. Up until the last 10-15 years, patients within each major subgroup were treated along broadly similar lines. Genetic abnormalities have been recognised in certain leukaemias for over 50 years; however, the recent explosion in our understanding of the frequency and complexity of molecular abnormalities in the leukaemias has 'opened the door' for the design of more targeted therapies with the expectation that their incorporation into therapeutic regimens will be associated with greater efficacy and less off-target toxicity.