BCL-W is dispensable for the sustained survival of select Burkitt lymphoma and diffuse large B-cell lymphoma cell lines
Research output: Contribution to journal › Article › peer-review
Authors
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
Details
Original language | English |
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Pages (from-to) | 356-366 |
Number of pages | 11 |
Journal | Blood Advances |
Volume | 4 |
Issue number | 2 |
Early online date | 27 Jan 2020 |
Publication status | Published - 28 Jan 2020 |