Therapeutic opportunities for counteracting apoptosis resistance in childhood leukaemia

Evasion of apoptosis is a hallmark of human cancers, for example in haematological malignancies. Apoptosis is an intrinsic cell death program that is crucial in maintaining tissue homeostasis, for example in the haematopoietic system where there is a high turnover rate of cells. As a result, a decrease in the rate of apoptosis as well as an increase in proliferation favours tumorigenesis as well as tumour progression. Further, the anti-leukaemic action of current treatment approaches, including chemo-, radio- or immunotherapy, critically relies on intact cell death programs in cancer cells. Therefore, defects in apoptosis pathways are frequently associated with the resistance to anticancer therapies. In recent years, the identification and characterization of the molecules and pathways that are involved in the regulation and execution of cell death in leukaemia and lymphoma cells, for example tumour necrosis factor-related apoptosis inducing ligand (TRAIL), 'inhibitor of apoptosis' (IAP) proteins and Bcl-2, have set the ground for the development of novel diagnostic tools and molecular therapeutics targeting apoptosis pathways in haematological malignancies.