Abstract
Dawson and colleagues showed that mixed-lineage leukaemia (MLL) fusion proteins, which commonly occur in aggressive leukaemia, associate with the bromodomain and extraterminal (BET) family of chromatin adaptor proteins. So, to target MLL-fusion-induced transcriptional responses, the authors treated mouse and human MLL-fusion leukaemia cells with a BET inhibitor, GSK1210151A, which induced cell cycle arrest and apoptosis. GSK1210151A treatment altered the expression of a common set of genes; in particular, BCL2, MYC and cyclin-dependent kinase 6 (CDK6) expression was reduced. The drug also improved the survival of mice with leukaemia induced by the expression of MLL-AF9 or MLL-AF4. In another paper, Mertz and colleagues treated various leukaemia and lymphoma cell lines with the BET inhibitor JQ1, which suppressed MYC expression and altered the expression of MYC target genes. Treatment with JQ1 resulted in cell cycle arrest and apoptosis, which was suppressed by exogenous expression of MYC from a BET regulation-resistant promoter. Finally, JQ1 reduced tumour growth of Burkitt's lymphoma cell and acute myeloid leukaemia cell xenografts. Together, these and the other recent papers that have investigated targeting the BET family indicate that this could be an efficacious strategy for targeting several types of leukaemia and, potentially, tumours overexpressing MYC.
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