BCL-W makes only minor contributions to MYC-driven lymphoma development

Diepstraten, ST; La Marca, JE; Chang, C; Young, S; Strasser, A; Kelly, GL

Author(s): Diepstraten, ST; La Marca, JE; Chang, C; Young, S; Strasser, A; Kelly, GL;
Details: Publication Year 2023-09,Volume 42,Issue #37,Page 2776-2781
Journal Title: Oncogene
Abstract: The BH3-mimetic drug Venetoclax, a specific inhibitor of anti-apoptotic BCL-2, has had clinical success for the treatment of chronic lymphocytic leukaemia and acute myeloid leukaemia. Attention has now shifted towards related pro-survival BCL-2 family members, hypothesising that new BH3-mimetic drugs targeting these proteins may emulate the success of Venetoclax. BH3-mimetics targeting pro-survival MCL-1 or BCL-XL have entered clinical trials, but managing on-target toxicities is challenging. While increasing evidence suggests BFL-1/A1 is a resistance factor for diverse chemotherapeutic agents and BH3-mimetic drugs in haematological malignancies, few studies have explored the role of BCL-W in the development, expansion, and therapeutic responses of cancer. Previously, we found that BCL-W was not required for the ongoing survival and growth of various established human Burkitt lymphoma and diffuse large B cell lymphoma cell lines. However, questions remained about whether BCL-W impacts lymphoma development. Here, we show that BCL-W appears dispensable for MYC-driven lymphomagenesis, and such tumours arising in the absence of BCL-W show no compensatory changes to BCL-2 family member expression, nor altered sensitivity to BH3-mimetic drugs. These results demonstrate that BCL-W does not play a major role in the development of MYC-driven lymphoma or the responses of these tumours to anti-cancer agents.
Publisher: NPG
Keywords: Humans; *Antineoplastic Agents/pharmacology/therapeutic use; Apoptosis; *Burkitt Lymphoma/drug therapy/genetics/pathology; Cell Line, Tumor; *Lymphoma, Large B-Cell, Diffuse/drug therapy/genetics/metabolism; Myeloid Cell Leukemia Sequence 1 Protein/genetics/metabolism; Proto-Oncogene Proteins c-bcl-2/genetics/metabolism
Research Division(s): Blood Cells And Blood Cancer
PubMed ID: 37567974
Publisher's Version: https://doi.org/10.1038/s41388-023-02804-5
Open Access at Publisher's Site: https://doi.org/10.1038/s41388-023-02804-5
Terms of Use/Rights Notice: Refer to copyright notice on published article.
Documents: s41388-023-02804-5.pdf - (1.54MB, application/pdf)

Creation Date: 2023-08-16 02:59:27

Last Modified: 2023-11-20 03:24:05