BCL-W is dispensable for the sustained survival of select Burkitt lymphoma and diffuse large B-cell lymphoma cell lines

Research output: Contribution to journalArticle

Authors

  • Sarah T Diepstraten
  • Catherine Chang
  • Lin Tai
  • Jia-Nan Gong
  • Ping Lan
  • Andreas Strasser
  • Gemma L Kelly

Colleges, School and Institutes

External organisations

  • Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia.
  • The Walter and Eliza Hall Institute for Medical Research, Parkville, VIC 3052, Australia.
  • Institute for Advanced and Applied Chemical Synthesis, Jinan University, Guangzhou, China; and.

Abstract

Dysregulated expression of BCL-2 family proteins allows cancer cells to escape apoptosis. To counter this, BH3-mimetic drugs that target and inhibit select BCL-2 prosurvival proteins to induce apoptosis have been developed for cancer therapy. Venetoclax, which targets BCL-2, has been effective as therapy for patients with chronic lymphocytic leukemia, and MCL-1-targeting BH3-mimetic drugs have been extensively evaluated in preclinical studies for a range of blood cancers. Recently, BCL-W, a relatively understudied prosurvival member of the BCL-2 protein family, has been reported to be abnormally upregulated in Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), and Hodgkin lymphoma patient samples. Therefore, to determine if BCL-W would be a promising therapeutic target for B-cell lymphomas, we have examined the role of BCL-W in the sustained growth of human BL- and DLBCL-derived cell lines. We found that CRISPR/CAS9-mediated loss or short hairpin RNA-mediated knockdown of BCL-W expression in selected BL and DLBCL cell lines did not lead to spontaneous apoptosis and had no effect on their sensitivity to a range of BH3-mimetic drugs targeting other BCL-2 prosurvival proteins. Our results suggest that BCL-W is not universally required for the sustained growth and survival of human BL and DLBCL cell lines. Thus, targeting BCL-W in this subset of B-cell lymphomas may not be of broad therapeutic benefit.

Bibliographic note

© 2020 by The American Society of Hematology.

Details

Original languageEnglish
Pages (from-to)356-366
Number of pages11
JournalBlood Advances
Volume4
Issue number2
Early online date27 Jan 2020
Publication statusPublished - 28 Jan 2020