BCL-W is dispensable for the sustained survival of select Burkitt lymphoma and diffuse large B-cell lymphoma cell lines.
Journal
Blood advances
ISSN: 2473-9537
Titre abrégé: Blood Adv
Pays: United States
ID NLM: 101698425
Informations de publication
Date de publication:
28 Jan 2020
28 Jan 2020
Historique:
received:
04
06
2019
accepted:
04
01
2020
entrez:
28
1
2020
pubmed:
28
1
2020
medline:
21
7
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31985804
pii: S2473-9529(20)31665-7
doi: 10.1182/bloodadvances.2019000541
pmc: PMC6988404
doi:
Substances chimiques
Apoptosis Regulatory Proteins
0
BCL2L2 protein, human
0
Proto-Oncogene Proteins c-bcl-2
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
356-366Informations de copyright
© 2020 by The American Society of Hematology.
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