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- W2318917032 abstract "The oncogene c-MYC is deregulated in multiple myeloma. Importantly, the activity of c-MYC is elevated in plasma cells in patients with myeloma compared to the premalignant state monoclonal gammopathy of undetermined significance, indicating a prominent role for c-MYC in myeloma pathogenesis. We earlier found the bone morphogenetic proteins induce apoptosis in myeloma cell lines and primary cells by SMAD-dependent downregulation of c-MYC. Repression of c-MYC by short hairpin RNA in myeloma cell lines has by others also been shown to induce apoptosis. We wanted to go one step further and study the role of c-MYC in primary myeloma cells. Transcriptional regulation by c-MYC requires heterodimerization of c-MYC and its obligate partner MAX. The small molecular inhibitor 10058-F4 disrupts the formation of such heterodimers and was used in vitro to test the dependency on c-MYC activity in primary myeloma cells and myeloma cell lines. The inhibitor induced apoptosis in a dose-dependent manner in the 22 primary samples tested. Apoptosis was induced in five of six cell lines tested. The sixth cell line, U266, does not express c-MYC, and was not sensitive to the inhibitor. Using the INA-6 myeloma cell line, we found that apoptosis induced by 10058-F4 correlated with downregulation of the anti-apoptotic protein Bcl-xL. We also found that apoptosis was induced by the inhibitor even in the presence of bone marrow stromal cells derived from myeloma patients. Our results further support that c-MYC is a potential target for therapy in multiple myeloma. Citation Format: Toril Holien, Thea K. Vatsveen, Hanne Hella, Anders Waage, Anders Sundan. Dependency on c-MYC in multiple myeloma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3130. doi:10.1158/1538-7445.AM2013-3130" @default.
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- W2318917032 date "2013-04-15" @default.
- W2318917032 modified "2023-09-27" @default.
- W2318917032 title "Abstract 3130: Dependency on c-MYC in multiple myeloma." @default.
- W2318917032 doi "https://doi.org/10.1158/1538-7445.am2013-3130" @default.
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