Journal article
BET inhibition induces apoptosis in aggressive B-cell lymphoma via epigenetic regulation of BCL-2 family members
SJ Hogg, A Newbold, SJ Vervoort, LA Cluse, BP Martin, GP Gregory, M Lefebure, E Vidacs, RW Tothill, JE Bradner, J Shortt, RW Johnstone
Molecular Cancer Therapeutics | AMER ASSOC CANCER RESEARCH | Published : 2016
Abstract
Targeting BET bromodomain proteins using small molecules is an emerging anticancer strategy with clinical evaluation of at least six inhibitors now underway. Although MYC downregulation was initially proposed as a keymechanistic property of BET inhibitors, recent evidence suggests that additional antitumor activities are important. Using the Eμ-Myc model of B-cell lymphoma, we demonstrate that BET inhibition with JQ1 is a potent inducer of p53-independent apoptosis that occurs in the absence of effects on Myc gene expression. JQ1 skews the expression of proapoptotic (Bim) and antiapoptotic (BCL-2/BCL-xL) BCL-2 family members to directly engage the mitochondrial apoptotic pathway. Consistent ..
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Awarded by Victorian Cancer Agency
Funding Acknowledgements
This work was supported by funding from the Leukemia Foundation of Australia (to S.J. Hogg, A. Newbold, G.P. Gregory, and M. Lefebure), the Cancer Therapeutics CRC (to S.J. Hogg and G.P. Gregory), the Royal Australasian College of Physicians (to G.P. Gregory), and the Arrow Bone Marrow Transplant Foundation (to M. Lefebure). J. Shortt is supported by funding from the Eva and Les Erdi/ Snowdome Foundation Victorian Cancer Agency Fellowship, and the Cancer Council Victoria. R.W. Johnstone is a senior principal research fellow (APP1077867) of the National Health and Medical Research Council of Australia (NHMRC) and is supported by an NHMRC program grant (APP454569), the Cancer Council Victoria and the Victorian Cancer Agency.