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Diffuse large B cell lymphoma (DLBCL) is a common and aggressive malignancy that accounts for 38-50% of lymphomas each year. There are two distinct subtypes of DLBCL: germinal center B cell-like (GCB) and activated B cell-like (ABC). Patients with ABC DLBCL have an inferior overall survival following multi-agent chemotherapy and respond differently to treatment compared to GCB DLBCL. In particular, the B cell receptor (BCR) signaling inhibitor, Ibrutinib, produced a response in 37% of DLBCL tumors with an ABC gene expression profile versus a 5% response in those tumors with a GBC gene expression profile. However, ABC cases with mutations in the BCR subunit, CD79B (along with a MYD88 mutation) produced an 80% response rate to ibrutinib. Using a protein-protein interaction-based proximity ligation assay, researchers at the National Cancer Institute (NCI), have discovered the molecular basis behind this difference in the ABC DLBCL tumor response rate: the presence of the My-T-BCR complex in double mutant cases contributes to ibrutinib disassembly, leading to an increase in drug resonsiveness.
This technology describes experimental methods to detect the My-T-BCR complex in patient biopsy samples and predict their responsiveness to ibrutinib and other inhibitors of BCR signaling.
The NCI seeks licensees and/or co-development partners to develop this technology toward commercialization.
Pre-clinical (in vivo)
Phelan JD, et. al. A multiprotein supercomplex controlling oncogenic signalling in lymphoma.
The process of gene expression is used by eukaryotes, prokaryotes, and viruses to generate the macromolecular machinery for life. Steps in the gene expression process may be modulated, including the transcription, RNA splicing, translation, and post-tran...