These alterations identify a mechanism of genetic instability in malignant B cells and may have been selected during lymphomagenesis for their role in altering BCL6 expression.
The 2016 WHO classification defines diffuse large B-cell lymphoma subtypes based on EBV infection and oncogenic rearrangements of MYC/BCL2/BCL6 as drivers of lymphomagenesis.
Because DLCL derive from germinal-center B cells, deregulated BCL-6 expression may contribute to lymphomagenesis by preventing postgerminal center differentiation.
Dacetuzumab-mediated CD40 signaling constitutively activated the nuclear factor-κB and mitogen-activated protein kinase signaling pathways producing the sustained downregulation of B-cell lymphoma 6 (BCL-6), an oncoprotein implicated in lymphomagenesis.
Translocations and somatic mutations are common genetic alterations of the BCL-6 gene on chromosome 3q27 in B-cell lymphoma, with implications for lymphomagenesis.
In siRNA experiments, DDX6 appeared not to be involved in NF-κB activation as frequently observed for genes promoting lymphomagenesis but was found to interfere with the expression of BCL6 and BCL2 in an NF-κB independent manner.
We identified ID3 mutations in lymphomas with chromosomal aberrations at cMYC and either BCL2 or BCL6 at a frequency intermediate between that of DLBCL and Burkitt lymphoma, hinting at a common pathway in lymphomagenesis for a subset of patients with DHL.
Together these results identify BCL6 as a potential driver of ETV6-RUNX1-mediated leukemogenesis, which could involve loss of BTG1-dependent suppression of ETV6-RUNX1 function.
We reveal a molecular mechanism controlling BCL6 stability and propose that mutations and deletions in FBXO11 contribute to lymphomagenesis through BCL6 stabilization.
Repression of AP-1 function by BCL-6 may be a key mechanism for how BCL-6 regulates gene expression to control inflammation, lymphocyte differentiation, and lymphomagenesis.
However, the significance of deregulated expression of BCL6 in lymphomagenesis and its effect on clinical outcomes of lymphoma patients have remained elusive.
Understanding the precise role of BCL6 in normal GC formation and in lymphomagenesis depends on the identification of genes that are direct targets of its transcriptional repression.
The frequency of these mutations, as well as their location in the proximity of BCL-6 regulatory sequences, suggest that they may play a role in AIDS-related lymphomagenesis.
Highlighting the central role of BCL6 in <i>MLL-</i>rearranged B-ALL, conditional deletion and pharmacological inhibition of BCL6 compromised leukemogenesis in transplant recipient mice and restored sensitivity to vincristine chemotherapy in <i>MLL-</i>rearranged B-ALL patient samples.