Previous studies have suggested that NF-kappaB activity is suppressed in germinal center and lymphoma B cells that express high levels of BCL-6, and yet the reason for this is unknown.
Double-color FISH with IgH (Y6) and BCL6 (cosB5-1) showed fusion of BCL6 and IgH genes on der(3)t(3;14) in all nine patients, suggesting that der(3) may play a critical role in the development of lymphoma carrying complex as well as standard t(3;14) translocations.
Patients with both MYC and BCL2 CNA had similar outcomes to those with classic double hit lymphoma or protein double expression lymphoma (MYC and BCL2/BCL6 coexpression).
The highest level of relative BCL-6 expression was observed in FCL (9.12 +/- 7.28) comparatively to the other lymphoma subtypes including DLBCL (2.53 +/- 1.82; P < 0.001), MCL (1.23 +/- 0.73), MZL (1.49 +/- 1.3), HD (1.60 +/- 1.00), TCL (1.75 +/- 1.64), but also RH (3.91 +/- 3.12) or NM (1.95 +/- 2.6).
Herein we show that the actions of EZH2 in driving GC formation and lymphoma precursor lesions require site-specific binding by the BCL6 transcriptional repressor and the presence of a non-canonical PRC1-BCOR-CBX8 complex.
Interestingly, 50% of the BCL-6 rearrangement positive lymphoma cases had coexisting gene rearrangements involving all of the aforementioned gene loci.
Simple karyotyping revealed key translocations involving MYC, BCL2, and BCL6 that have impacted lymphoma classification in the World Health Organization classification scheme.
Several experiments and mouse models mimicking BCL6 translocation occurring in human lymphoma have demonstrated the oncogenic role of BCL6 and constitute a rational to consider BCL6 as a new therapeutic target in NHL.
Reasoning that disruption of POZ domain-mediated interactions may be an effective route to antagonizing the effects of BCL-6 in lymphoma, we screened a library for peptide aptamers that specifically bind to BCL-6 POZ and not the POZ domains of related proteins and describe here the first of these reagents, Apt48.
Following a broad panel of immunohistochemical stains, the strong positive staining of the spindle cells for LCA (CD45), CD20, and Bcl-6 confirmed the diagnosis of follicle center cell lymphoma.
Therefore, tandem targeting of the overlapping BCL6 and p53 transcriptional programs can correct aberrant survival pathways in DLBCL and might provide an effective therapeutic approach to lymphoma therapy.
Mutations of BCL-6 proto-oncogene, a zinc finger transcription factor implicated in lymphoma development, represent a histogenetic marker of B cell transit through the germinal center (GC) and occur frequently in B cell malignancies derived from GC or post-GC B cells.
Reverse transcriptase-mediated polymerase chain reaction revealed chimeric mRNA consisting of two non-coding exons 1a/1b of IL-21R and coding exons of BCL6 in both lymphoma cells.
Analysis of the bcl6 noncoding first exon showed somatic mutations in two of four cases analyzed, as would be expected in lymphoma deriving from the germinal center.
Follicular lymphoma without t(14;18) and with BCL-6 rearrangement: a lymphoma subtype with distinct pathological, molecular and clinical characteristics.
The heterogeneity in partner sites is distinct from other lymphoma subgroups and may suggest that the genetic events are not uniform among patients with BCL6 rearrangements.