Project description:B-cell receptor (BCR) signaling promotes the survival of malignant B cells, such as Burkitt’s lymphoma (BL) and the activated B-cell-like subtype of diffuse large B cell lymphoma (ABC-DLBCL). In contrast to ABC DLBCL, where malignant cells require chronic activation of the BCR for their survival, BL cells are dependent on tonic BCR signaling that is antigen-independent. Elucidation and systematic comparison of tonic and activated BCR signaling led to the identification of novel signaling effectors, among them ACTN4 and ARFGEF2, which were identified as regulators of BL cell survival. As tonic and activated BCR signaling are relevant for important aspects of B cell biology, our study helps in gaining an understanding of BCR-induced processes not only in malignant but potentially also physiological settings.

2016-05-09 | PXD003492 | Pride

DNA-replication stress induced transcriptome of Human Burkitt’s lymphoma cells identifies MBD1 as a novel suppressor of Germinal center derived B-lymphomagenesis [ChIP]

Project description:Germinal center (GC) derived B-lymphomas (GCDBL) are concomitantly generated with high-affinity B cells during humoral immune response. Among GCDBLs are Burkitt’s lymphoma (BL), diffuse large B cell lymphoma (DLBCL), and Multiple myeloma (MM), which originate from distinct GC compartments. Whether specific transcription factors work in GCs to suppress the GCBLD is elusive.

2026-08-12 | GSE242935 | GEO

DNA-replication stress induced transcriptome of Human Burkitt’s lymphoma cells identifies MBD1 as a novel suppressor of Germinal center derived B-lymphomagenesis [RNA]

2026-08-12 | GSE242375 | GEO

HSP90 promotes Burkitt lymphoma cell survival by maintaining tonic B cell receptor signaling

Project description:Burkitt’s lymphoma (BL) is an aggressive B-cell neoplasm that is currently treated by intensive chemotherapy in combination with anti-CD20 antibodies. Because of their toxicity, current treatment regimens are often not suitable for elderly patients or for patients in developing countries where BL is endemic. Hence, there is a need for targeted therapies. In this study, we performed a compound screen in 17 BL cell lines to identify small molecule inhibitors affecting cell survival. We observed that, among other compounds, inhibitors of heat shock protein 90 (HSP90) induce apoptosis in BL cells in vitro at concentrations that did not affect normal B cells. By global proteomic and phosphoproteomic profiling, we found that in BL, HSP90 inhibition compromises activity of the pivotal B cell antigen receptor (BCR)-proximal effector spleen tyrosine kinase (SYK), which we identified as an HSP90 client protein. Consistently, expression of constitutively active TEL-SYK counteracted the apoptotic effect of HSP90 inhibition. Hence, our study provides a molecular rationale for the use of HSP90 inhibitors in the treatment of BL by demonstrating that HSP90 inhibition interferes with tonic BCR signaling and thus impairs BL cell survival.

2017-01-02 | PXD004181 | Pride

ViPOR in Relapsed/Refractory B-Cell Lymphoma

Project description:ViPOR in Relapsed/Refractory B-Cell Lymphoma

| PRJNA1090979 | ENA