Furthermore, this case is unique in the direct demonstration of the histologic and clinical progression of a human lymphoma associated with the sequential rearrangement of the bcl-2 gene and the c-myc oncogene.
These included 12 of 20 cases of nodular follicular center cell lymphoma (nine small cleaved cell, one mixed small and large cell, and two large cell types). bcl-2 translocation was detected in only three of 45 cases of diffuse B-cell lymphoma, and cases of AIDS-related malignant lymphoma, monocytoid B-cell lymphoma, and mantle zone lymphoma were all negative.
There were 47 DTHLs, 36 cases with MYC and BCL2 and/or BCL6 extra signals (ES) and/or rearrangements (ES group, excludes DTHLs), 9 with MYC rearrangements only (single-hit lymphoma), and 95 with no MYC abnormalities (NM).
PCR is a rapid and easy technique that can detect the abnormal rearrangement of the bcl-2 gene and clonal IgH rearrangement, indicating the presence of lymphoma.
Accordingly, BCL2 mutations can affect antiapoptotic Bcl-2 function, are associated with increased activation-induced cytidine deaminase expression, and correlate with increased risk of transformation and death due to lymphoma.
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.
We report eight new cases of persistent polyclonal B-cell lymphocytosis, which displayed a misleading bone marrow histological pattern, that is, intravascular B-cell infiltrate, constantly associated with Bcl-2 immunohistostaining, as seen in some lymphoma.
BCL-2/IgH transcripts were demonstrated in 16 follicular center cell lymphoma cases (five high, 11 low) and were not present in any of the five non-neoplastic lymph nodes.
Thus, constitutive IP<sub>3</sub> signaling in lymphoma and leukemia cells is not only important for cancer cell survival, but also represents a vulnerability, rendering cancer cells dependent on Bcl-2 to limit IP<sub>3</sub>R activity.
A graft-versus-lymphoma effect was demonstrable and quantitative PCR for bcl-2/IgH may allow better accuracy in scheduling post-allograft rituximab and/or donor lymphocyte infusions.
A bcl-2/JH gene fusion was detected only in three lymphoma subgroups: 13 of 33 centroblastic-centrocytic (39%), 2 of 37 centroblastic (6%), and 2 of 27 immunocytic (8%) were positive.
Overexpression of the pro-survival member BCL-2 is a well-established mechanism contributing to oncogenesis and chemoresistance in several cancers, including lymphoma and leukemia.
Furthermore, ectopic expression of Bcl-X(L) (but not Bcl-2) in two B-lymphoma cell lines decreased their sensitivity to parthenolide-induced apoptosis.
These data indicate that primary cutaneous lymphomas of B-cell origin share morphological and phenotypic similarities with the nodal B-cell lymphomas of follicular histotype, are proliferating, and express in 45% of cases clear monoclonal immunoglobulin light chain; the molecular analysis confirms the B-cell derivation and the monoclonal nature of this neoplasia; it also shows that neither bcl-2 nor c-myc oncogenes are involved and that no inappropriate rearrangements of the T-cell receptor genes are found in this lymphoma.
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).
Treatment of lymphoma-bearing SCID mice with G3139 for two consecutive days prior to each rituximab dose resulted in better disease control and survival than treatment with either agent alone or controls.