On the basis of evidence that the pro-inflammatory cytokine, interleukin 6 (IL6), and the survival-enhancing oncoprotein, B cell leukemia 2 (BCL2), have critical roles in the natural history of WM, we hypothesized that the enforced expression of IL6 and BCL2 in mice unable to perform immunoglobulin class switch recombination may result in a lymphoproliferative disease that mimics WM.
By direct sequencing, we found clonally represented BCL2 mutations in 2/16 (13%) of t(14;18) negative FLs, 2/16 (13%) HIV-DLBCLs, 1/9 (11%) of Richter's syndrome DLBCL, 1/17 (6%) of post-transplant lymphoproliferative disorders and 1/2 (50%) common-variable immunodeficiency-associated DLBCL.
Bcl-2 is an apoptosis regulating protein, overexpression of which is associated with chemotherapy resistant disease, aggressive clinical course, and poor survival in patients with B-cell lymphoproliferative disorders.
The results suggested that BCL2 protein expression is regulated at the transcriptional level in normal B cells and in the neoplastic cells in most B-cell lymphoproliferative disorders.
Because the humanized anti-CD20 antibody, rituximab, has antitumor activity in patients with PTLD and stimulates apoptosis in some lymphoid cell lines, we sought to determine whether Bcl-2 antisense treatment potentiates the antitumor effects of rituximab in EBV-associated lymphoproliferative disease in vitro and in vivo.
NFkappaB activation may inhibit apoptosis through the transactivation of genes such as Bcl-2 and may therefore be an important mechanism in indolent lymphoproliferative disorders, including WM.
These data indicate that t(14;18) and bcl-2 over-expression in lymphoid cells are frequent in chronic HCV infection and suggest that this event may contribute to the pathogenesis of HCV-related lymphoproliferative disorders.
Furthermore, treatment of LCL-bearing severe combined immunodeficient mice with Bcl-2 antisense but not control oligodeoxynucleotides completely prevented or significantly delayed the development of fatal EBV-positive lymphoproliferative disease in vivo.
We used PCR to amplify bcl-2 and IgH rearrangements in DNA from patients with lymphoproliferative disorders and analyzed the products in parallel by gel electrophoresis and flow cytometry, which detected PCR products incorporating fluoresceinated oligonucleotide primers by sequence-specific capture to oligonucleotide-coated magnetic beads.
Rearrangement of the rheumatoid factor-related germline gene Vg and bcl-2 expression in lymphoproliferative disorders in patients with Sjögren's syndrome.
The combination of chromosomal translocations associated with bcl-2 rearrangement [t(14;18)] and c-myc rearrangement [t(8;14), t(8;22), or t(2;8)] has infrequently been detected in lymphoproliferative disorders.
We studied 115 cases of lymphoproliferative disease with the polymerase chain reaction for bcl-2 oncogene using biotin and radiolabeled probes to the major breakpoint and minor cluster regions.
However we also found bcl-2 protein in normal T- and B-lymphoid cells and in a variety of lymphoproliferative disorders in which the 14;18 translocation is not present.