BCL-W is dispensable for the sustained survival of select Burkitt lymphoma and diffuse large B-cell lymphoma cell lines
- Author(s)
- Diepstraten, ST; Chang, C; Tai, L; Gong, JN; Lan, P; Dowell, AC; Taylor, GS; Strasser, A; Kelly, GL;
- Details
- Publication Year 2020-01-28,Volume 4,Issue #2,Page 356-366
- Journal Title
- Blood Advances
- Publication Type
- Journal Article
- 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.
- Publisher
- ASH
- Research Division(s)
- Blood Cells And Blood Cancer
- PubMed ID
- 31985804
- Publisher's Version
- https://doi.org/10.1182/bloodadvances.2019000541
- Open Access at Publisher's Site
https://doi.org/10.1182/bloodadvances.2019000541- NHMRC Grants
- NHMRC/1124784, NHMRC/1066770, NHMRC/1057852, NHMRC/1124907, NHMRC/1124788, NHMRC/1088703,
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2020-05-04 11:46:50
Last Modified: 2020-05-04 01:53:11