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Comparative gene expression analysis in OCI-LY8 isogenic cell lines with SETD1B mutation or WT control.

GSE273153 Homo sapiens Expression profiling by high throughput sequencing 6 samples Submitted 2024/08/23 Platform GPL20301
Summary
The translocation t(14;18) activates BCL2 and is considered the initiating genetic lesion in most follicular lymphomas (FL). Surprisingly, FL patients fail to respond to the BCL2 inhibitor, Venetoclax. We show that mutations and deletions affecting the histone lysine methyltransferase SETD1B (KMT2G) occur in 7% of FLs and in 16% of diffuse large B cell lymphomas (DLBCL). Deficiency in SETD1B confers striking resistance to Venetoclaxand to an experimental MCL-1 inhibitor. SETD1B also acts as a tumor suppressor andcooperates with loss ofKMT2Din lymphoma development in vivo. Consistently, loss of SETD1B in human lymphomas typically coincides with loss of KMT2D. Mechanistically, SETD1B is required for the expression of several pro-apoptotic BCL2 family proteins. Conversely, inhibitors of the KDM5 histoneH3K4demethylases restore BIM and BIK expression and synergize with Venetoclax inSETD1B-deficient lymphomas.
Published in
SETD1B mutations confer apoptosis resistance and BCL2 independence in B cell lymphoma
Portelinha A, Wang S, Parsa S et al. · The Journal of experimental medicine 2024 · PMID 39235528 · doi:10.1084/jem.20231143
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Also filed as BioProject PRJNA1140256 and SRA study SRP522289. Searching any of these in the dataset finder brings you back here.

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