Dysregulated bcl-2 expression, secondary to (14;18) chromosomal translocation, seems to promote the development of follicular lymphomas, and recent findings of bcl-2 protein in several solid tumors suggest that it might contribute to the genesis of many other neoplasms. bcl-2 is also highly expressed in normal proliferative endometrium and markedly down-regulated in secretory endometrium, which suggests that its expression is estrogen regulated.
Follicular lymphoma (FL) is the most frequent indolent lymphoma in the Western world and is characterized in almost all cases by the t(14;18) translocation that results in overexpression of BCL2, an anti-apoptotic protein.
In conclusion, we assume the incidence of t(14;18) in HL associated with FL is higher than previously believed and BCL2 expression derived from t(14;18) may play a role in the pathogenesis of HL associated with FL.
These results suggest a diverse portfolio of genetic alterations that may induce or regulate BCL2 expression or promote pathogenesis of t(14;18)-negative FL as well as a less specific but increased crosstalk with the microenvironment that may compensate for the lack of N-glycosylation.
Numerous microRNAs were found to be differentially expressed between FL(BCL2+/BCL6+) and FL(BCL2-/BCL6+), as well as diffuse FL, when compared to typical cases of FL.
For example, overexpression of Bcl-2 blocks apoptosis and this contributes to the accumulation of cells in follicular lymphomas and chronic lymphocytic leukemia.
Follicular lymphoma (FL) shows co-expression of B-cell lymphoma 2 (BCL2) and CD10, whereas downexpression of CD10 is occasionally experienced in gastrointestinal (GI) FL with unknown significance.
Scanning densitometry of Western blots demonstrated that the myeloid U-937 cells express low levels of bcl-2 (RD = 0.008), whereas the follicular lymphoma RL-7 expressed very high levels (RD = 3.084).
While none of the DXM-resistant cell lines lacked Bcl-2 expression, several pre-B or FL lines that expressed [correction of expessed] Bcl-2 were sensitive to DXM.
All patients from Group A showed IHC positive reaction on FCL remnant (small cleaved cells) but only 2 (18%) were positive in DLBCL areas, suggesting either the loss of the bcl-2 expression on the transformed lymphoma, or, alternatively, the development of a second disease when the first lymphoma transforms.
However, bcl-2 expression in pediatric follicular lymphoma identifies a subset of patients in whom disease is often disseminated at clinical presentation and is more refractory to combination chemotherapy.
The expression of bcl-2 protein has been observed in most follicular lymphomas and in approximately 25% of high-grade non-Hodgkin's lymphomas, as well as in solid tumors such as carcinomas of the lung, prostate, and nasopharynx.
However, as bcl-2 expression in the GC alone is thought to be insufficient for FL development, we next monitor simulated IgV region mutations to determine the emergence times of key mutants displaying aberrant N-glycosylation motifs recurrently observed in human FL IgV regions.
The t(14,18) chromosomal translocation that occurs in human follicular lymphoma constitutively activates the BCL2 gene and disrupts control of apoptosis.
It is considered that BCL2 overexpression underscores the development of the majority of cases of FL and their transformation to more aggressive lymphoma [known as transformed FL (tFL)].
The Epstein-Barr virus (EBV) genome contains an open reading frame, BHRF1, that encodes a presumptive membrane protein with sequence similarity to the proto-oncogene bcl2, which is linked to human B-cell follicular lymphoma.
We correlated this with the immunohistochemical expression of CD10, bcl2 and bcl6, markers which are usually expressed by the neoplastic cells in follicular lymphomas.
This oligo selectively inhibited Bcl-2 protein expression and induced growth inhibition in t(14;18)-positive transformed follicular lymphoma (FL) cell lines.
In contrast to other FL, FL3B frequently lack CD10 expression (approximately 50% of cases), show lower probability of BCL2 expression (69% positive) and increased TP53 expression (31% positive).
Downregulation of BCL-2 and light-chain switch have rarely been reported in previous cases of FL transformation involving c-MYC, suggesting that additional t(2;8) translocation may play a role in these events.
Histopathological examination revealed FL of grade 1-2 with a follicular pattern and with strong expression of germinal center markers and B-cell lymphoma 2 (BCL2).
The selectivity and efficacy of all sense ODNs tested provide support for the development of therapeutic ODNs targeting the bcl-2-IgH antisense transcript expressed in human follicular lymphomas.