Since its discovery in follicular lymphoma cells at the breakpoint t(14;18), Bcl-2 has been studied extensively in many basic and clinical science settings.
PCR provided evidence of t(14; 18) in only 2 HD cases (6%), both of which were associated with a prior history of follicular lymphoma, and both of which were among the 7 cases (22%) with strong bcl-2 expression in Hodgkin cells.
Interestingly, all of these 5 cases lackedBCL2 overexpression as determined by immunohistochemistry, against 3 of 35 rearrangement-positive follicular lymphomas.
By N-PCR, a total of 42 (51%) FL cases showed BCL-2 rearrangement: 28 (34%) for major breakpoint region (MBR) and 14 (17%) for minor cluster region (mcr).
To evaluate the long-term results of high-dose therapy (HDT) in follicular lymphoma, with specific emphasis on the prognostic significance of polymerase chain reaction (PCR)-detectable Bcl-2/IgH rearrangements.
These mutations, which result in the replacement of a single tyrosine in the SET domain of the EZH2 protein (Tyr641), occur in 21.7% of GCB DLBCLs and 7.2% of FLs and are absent from ABC DLBCLs.
Follicular lymphoma (FL) is an indolent, mature B-cell neoplasm classically characterised by the t(14;18)(q32;q21) with constitutive overexpression of the anti-apoptotic protein, BCL2.
These data show that bcl-2 translocation is present in 57% of follicular lymphomas in Chinese patients, and support the notion that bcl-2 translocation is a consistent marker for follicular lymphomas irrespective of ethnic differences.
In this patient's leukemic cells, the breakpoint of the t(14;18) translocation occurred in the major breakpoint-cluster region of the BCL2 gene and became linked to the JH4 joining-region gene segment of the immunoglobulin heavy-chain locus on the 14q+ chromosome as previously observed in follicular lymphoma.
Translocation t(14;18)(q32;q21) and/or BCL-2-IGH gene rearrangements were the genomic alterations most frequently observed: 50% of S-DLBCL and 30% of dn-DLBCL.
The present data support the hypothesis that BCL-2-positive and BCL-2-negative follicular lymphomas (grades 1-3A) represent a homogenous group with different initial but several common additional molecular pathways.
Two of eight (25%) cases of follicular lymphoma but only one of the 34 (2.9%) cases of diffuse B-cell lymphoma had bcl-2 rearrangement that was detected by pFL-1 probe.
This study evaluates the utility of fluorescence-based polymerase chain reaction (PCR) and PCR-SSCP methodologies to monitor the clonal relatedness of cells with bcl-2 major break point region (mbr)/JR fusion sequences in sequential samples from patients with follicular lymphoma (FL).
EZH2 mutations were frequently associated with the presence of BCL2 rearrangement (BCL2-R) in both the FL (28% of BCL-R cases versus 0% of BCL2-WT cases, p<0.05) and GCB-DLBCL groups (33% of BCL2-R cases versus 4% of BCL2-WT cases, p<0.04), and across all lymphoma types excluding BL (27% of BCL2-R cases versus 3% of BCL2-WT cases, p<0.003).
These data suggest that Bcl-2 overexpression leads to the induction of activated signal transducer and activator of transcription 3 (STAT3) and to the induction of SOCS3, which may contribute to the pathogenesis of follicular lymphoma.
Polymerase chain reaction (PCR) protocols have been developed to detect the t(14;18) translocation, which juxtaposes the bcl-2 proto-oncogene to the Ig heavy-chain (IgH) gene in 85% of follicular lymphomas and monoclonal rearrangements of the IgH gene in B-cell NHL that lack bcl-2 rearrangements.
To characterize PCFL and PCMZL more clearly and to define criteria helpful for the differential diagnosis, we compared expression of immunohistochemical markers [LIM-only transcription factor 2 (LMO2), human germinal centre-associated lymphoma (HGAL), stathmin 1 (STMN1), activation-induced cytidine deaminase (AID), myeloid cell nuclear differentiation antigen (MNDA)] and the presence of cytogenetic abnormalities described previously in nodal follicular lymphoma [B cell lymphoma 2 (BCL2) and BCL6 breaks, 1p36 chromosomal region deletion (del 1p36)] in a series of 48 cutaneous follicular and marginal zone lymphomas [cutaneous follicular lymphoma (CFL) and cutaneous marginal zone lymphoma (CMZL)].
BCL6-mediated suppression of BCL2 is lost in FL and DLBCL, where the 2 proteins are pathologically coexpressed, because of BCL2 chromosomal translocations and other mechanisms, including Miz1 deregulation and somatic mutations in the BCL2 promoter region.
The bcl-2 breakpoint site was determined in 247 previously untreated patients (49% men; median age 52 years) with indolent FL (155 grade I, 83 grade II, and 8 grade III) to correlate it with pretreatment characteristics, response, and outcome.
Detection and quantification of MBR/JH2 t(14;18) BCL-2 gene rearrangement in follicular lymphoma using a combined real-time polymerase chain reaction assay.