Poster Presentation 31st Lorne Cancer Conference 2019

Loss of BCL-W does not impact the survival of human Burkitt and diffuse large B cell lymphoma cells (#157)

Sarah T Diepstraten 1 2 , Catherine Chang 1 , Andrew J Kueh 1 2 , Stephen Wilcox 1 2 , Jia-Nan Gong 1 2 , Andreas Strasser 1 2 , Gemma L Kelly 1 2
  1. Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia
  2. Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia

The dysregulated expression of the BCL-2 family of proteins allows cancer cells to escape apoptosis. BCL-W is an understudied member of the pro-survival BCL-2 protein family, and has recently been reported to be upregulated in Burkitt lymphoma (BL) and diffuse large B cell lymphoma (DLBCL) patient samples, and furthermore to contribute to the survival of BL cell lines[1]. In addition, BCL-W has been identified in a screen for factors conferring resistance to BH3 mimetics, a promising class of anti-cancer drugs which can induce apoptosis[2]. In light of these studies, we sought to investigate the role of BCL-W in the growth and survival of human BL and DLBCL cell lines. Detectable expression levels of BCL-W were observed by Western blotting in three of five lymphoma cell lines tested. Utilising CRISPR/Cas9 gene editing to disrupt this expression, we found that loss of BCL-W did not lead to apoptosis in BL and DLBCL cells. Additionally, BCL-W loss had no impact on the sensitivity of these tumour cells to a range of BH3 mimetics targeting other pro-survival proteins, including BCL-2 and MCL-1. Our results suggest that, in contrast to previous reports in the literature, BCL-W is dispensable for the sustained growth and survival of human BL and DLBCL cell lines. Thus, BCL-W is not an effective target for novel BH3 mimetics, or other anti-cancer therapies for this subset of B cell lymphomas.

  1. Adams et al. 2017. J Clin Invest.127(2):635-650.
  2. Soderquist et al. 2018. Nat Commun. 9(1):3513.