Dysregulation of BCL-2 Family Proteins by Leukaemia Fusion Genes

Abstract The genomic lesions that characterise acute lymphoblastic leukaemia in childhood include recurrent translocations that result in the expression of fusion proteins. These translocations typically involve the rearrangement of genes encoding tyrosine kinases, including receptor tyrosine kinase, cytokine receptors and transcription factors. These confer phenotypic changes that are the hallmarks of malignant transformation, including unrestricted proliferation and a relative resistance to apoptosis. In this review, we explore the molecular mechanisms that link these fusions to the control of cell death. More specifically, we look at the regulation of the BCL-2 family of proteins by these fusion genes to prevent the activation of apoptotic effectors, BAX and BAX, and promote cell survival.