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BCL-W is dispensable for the sustained survival of select Burkitt lymphoma and diffuse large B-cell lymphoma cell lines.
| Content Provider | Scilit |
|---|---|
| Author | Diepstraten, Sarah T. Chang, Catherine Tai, Lin Gong, Jia-Nan Lan, Ping Dowell, Alexander C. Taylor, Graham S. Strasser, Andreas Kelly, Gemma L. |
| Copyright Year | 2020 |
| Description | 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. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6988404/pdf |
| Ending Page | 366 |
| Page Count | 11 |
| Starting Page | 356 |
| DOI | 10.1182/bloodadvances.2019000541 |
| Journal | Blood advances |
| Issue Number | 2 |
| Volume Number | 4 |
| Language | English |
| Publisher | American Society of Hematology |
| Publisher Date | 2020-01-27 |
| Access Restriction | Open |
| Subject Keyword | Hematology Apoptosis Lymphoma Bh3 Prosurvival Proteins Mimetic Drugs Targeting Journal: Blood advances (Vol- 41, Issue- 2) |
| Content Type | Text |
| Resource Type | Article |