All FL tested were bcl-6+ (19) and CD138- (22) with 16/19 also bcl-2 and CD10+ (classic phenotype), one bcl2+, CD10- (grade III) and two bcl2-, CD10+ (grade II or III).
In this retrospective study, we assess 157 patients with MYC/BCL2 DHL including 108 patients with de novo disease and 49 patients with a history of FL or rarely other types of low-grade B-cell lymphoma.
We developed a mouse model that recapitulates the FL hallmark t(14;18) translocation, which results in constitutive activation of antiapoptotic protein B cell lymphoma 2 (BCL2) in a subset of B cells, and applied a combination of molecular and immunofluorescence approaches to track normal and t(14;18)(+) memory B cells in human and BCL2-overexpressing B cells in murine lymphoid tissues.
Here, we show that FL cells display a different pattern of expression of bcl-2 family proteins from normal germinal center (GC) B cells that are thought to be their normal counterpart.
These findings suggest that the der(3)t(3;18)(q27;q21) involving BCL2 and BCL6 had a crucial role in the pathogenesis of FL with t(3;14;18)(q27;q32;q21).
BCL2 expression from altered allele also keeps its expression at the germinal center stage where normal counterpart cells down-regulate BCL2 expression, and makes cells to resist apoptosis, leading to development of follicular lymphoma.
Three cases corresponded to FL with the minor breakpoint in the bcl-2 gene and these patients had a favorable clinical evolution, whereas the 4 patients with p53 mutations and the major breakpoint had a bad clinical outcome with morphologic transformation to high-grade lymphoma in three cases.
Rearrangement of the bcl-2 gene at the MBR (major breakpoint region) locus with the immunoglobulin heavy-chain joining region has been reported in a high proportion of follicular lymphomas.
Follicular lymphomas that lack a t(14;18) were segregated into two subgroups with distinct cytogenetic, phenotypic and possibly clinical features: one with BCL2 protein overexpression not related to an IGH/BCL2 rearrangement and a second without BCL2 overexpression.
BCL2 protein expression pattern was analysed in 26 cases of t(14;18) negative follicular lymphoma [determined by fluorescence in situ hybridisation (FISH)], using antibodies against two-different epitopes, i.e., the widely-used antibody BCL2/124 and an alternative antibody E17.
This study was undertaken to determine the pattern of Bcl-2, CD10 and Bcl-6 expression in relation to t(14;18) translocation in follicular lymphoma from a cohort of a multi-ethnic Asian population.
The histone lysine methyltransferase (MT) Enhancer of Zeste Homolog 2 (EZH2) is considered an oncogenic driver in a subset of germinal center B-cell-like diffuse large B cell lymphoma (GCB-DLBCL) and follicular lymphoma due to the presence of recurrent, monoallelic mutations in the EZH2 catalytic domain.
In the present study, bcl-2 was rearranged in 30% (11 of 37) of follicular lymphomas and 19% (11 of 58) of diffuse lymphomas of follicle center cell lineage.
Conventional cytogenetic or fluorescence in situ hybridization studies performed in 3 cases showed t(14;18)(q32;q21) or IGH-BCL2, supporting the diagnosis of FL.
The MCL1 gene, recently identified in a myeloid leukemia cell line, has sequence similarity to BCL2, the gene at the t(14;18) translocation in follicular lymphoma.
We have previously reported an overexpression of Smad1 in follicular lymphoma (FL) cells, which are characterized by the t(14;18) bcl2/IgH translocation.
As opposed to adult cases, pediatric FL is characterized by a high-grade histology, low-stage disease, a lower frequency of both bcl-2 protein expression and BCL2 gene rearrangement, and a more favorable prognosis.
Recently, in situ follicular neoplasia (ISFN), characterized by accumulations of immunohistochemically strongly BCL2-positive, t(14;18)+ clonal B cells confined to germinal centers in reactive lymph nodes, has been identified as a precursor lesion of FL with low risk of progression to manifest FL.
We therefore suggest that the relatively low incidence of FL in Asian populations is caused not by a lower frequency of bcl-2 rearrangements in healthy populations but by distinct molecular pathways developing in different geographic regions that nonetheless culminate in FL, which is morphologically similar but molecularly distinct.