Having established a lymphoma model the cells were treated with antisense oligonucleotides to the first open reading frame of the BCL-2 gene prior to inoculation of the SCID mice.
These results demonstrate: 1) bcl-2 protein is expressed in a small portion of cutaneous B-cell lymphomas; 2) bcl-2 protein expression is significantly more frequent in secondary than in primary cutaneous B-cell lymphoma; 3) only approximately one-third of cases expressing the bcl-2 protein are characterized also by the t(14;18). bcl-2 protein expression might indicate that the cutaneous manifestation of the lymphoma represents a secondary spread from a node-based lymphoma.
Quantitative variation in human BCL2 mutation frequency is extensive, and BCL2 mutation frequency rises with age, concordant with increased risk for lymphoma.
We used a battery of antibodies directed against the following: cytokeratins (CKs) 5, 10, 17, and 19, actin, cell-adhesion proteins (desmoplakins, desmogleins), markers of terminal epidermal differentiation (filaggrin, involucrin and loricrin), markers of proliferation (PCNA, MIB, K6,16), a marker of endocytosis (clathrin) and markers of cell growth, (transforming growth factor [TGF-alpha]) and B-cell leukemia/lymphoma-2 [bcl-2].
In particular, the recognition of chromosomal translocations which have activated the BCL1 and BCL2 proto-oncogenes have strong associations with specific types of non-Hodgkin's malignant lymphomas such as mantle cell lymphoma and follicular center cell lymphoma, respectively.
This study showed that it is feasible to use the Bcl2/JH PCR technique for residual cell lymphoma detection in patients undergoing intensive chemotherapy or BM transplantation.
The most common translocation in human lymphoma, t(14;18)(q32;q21), recombines the bcl-2 gene with the immunoglobulin (Ig) heavy-chain locus leading to the production of high levels of chimeric RNAs and the resulting 26 kDa bcl-2 protein.
In the present study, we investigated Bcl-2's mechanism of action by determining the effect of Bcl-2 on intracellular Ca2+ fluxes in the WEHI7.2 mouse lymphoma cell line, which does not express Bcl-2, and its stable transfectant, W.Hb12, which expresses a high level of Bcl-2.
Although Bcl-2 protein can prevent or delay apoptosis of lymphoma and leukemia cells, exposed to multiple cytotoxic agents, its antagonism of GC-induced apoptosis appears most critical in conferring resistance to corticosteroids.
Immunohistochemical analysis showed either a monotypic expression of immunoglobulin light chain or a positive staining with anti-bcl-2 antibodies in three and four samples, respectively, of lymphoma.
In order to clarify the effects of Epstein-Barr virus (EBV) infection on apoptosis and proliferative activity of non-Hodgkin's lymphoma, 135 Japanese lymphoma cases were investigated for the presence of viral RNA and its correlation with bcl-2 protein (Bcl-2) expression.
To study the BCL2 amplification we performed comparative genomic hybridization (CGH), Southern blot hybridization, Western analysis, immunohistochemistry, metaphase fluorescence in situ hybridization, and chromosome analysis on 26 cases of diffuse large B-cell lymphoma (large noncleaved cell lymphoma).
These data indicate that the combined PCR analysis of IgH and BCL2 rearrangements can confirm a cytologic diagnosis of lymphoma in FNAs while, due to the occurrence of both false-positive and false-negative results, it is of limited value in the distinction between follicular lymphoma and lymphoid hyperplasia without morphologic or clinical support.
Ninety-seven per cent (36/37) of follicular lymphomas expressed bcl-2 protein in all three grades, manifesting in the small cell (grade 1) through to the large cell (grade 3). p53 protein expression showed a pattern of increasing immunostaining with progression towards the high-grade follicular lymphoma: grade 1 = 6 per cent (1/16); grade 2 = 48 per cent (10/21); grade 3 = 100 per cent (6/6).
These results suggest that decreased expression of C-MYC and BCL2 may play a role in the molecular events that initiate and are responsible for the growth inhibition of Raji lymphoma xenografts by MP.
In both human lymphoma and carcinoma, BCL2 expression contributes to the neoplastic development by preventing normal turnover due to programmed cell death.
The possibility of combining antisense therapy such as BCL-2 antisense with chemotherapy will probably provide an interesting means of overcoming tumour cell resistance to chemotherapy in lymphoma and a range of other high BCL-2 expressing malignancies.