Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0079731 (B-cell lymphoma)
 16,671 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the relative importance of class I and class II major histocompatibility complex (MHC) immunoregulation in the control of T- and B-cell lymphomas induced by murine leukemia virus. Previously, we have described a mink cell focus-inducing (MCF) murine leukemia virus, MCF 1233, which induces not only lymphoblastic T-cell lymphomas but also follicle center cell or lymphoblastic B-cell lymphomas. We now report that the outcome of neonatal infection with MCF 1233 in H-2-congenic C57BL/10 and C57BL/6 mice is decisively influenced by the H-2 I-A locus. A total of 64% of H-2 I-Ak, d mice [B10.BR, B10.D2, B10.A(2R), B10.A(4R), and B10.MBR] developed T-cell lymphomas after MCF 1233 infection (mean latency, 37 weeks). In contrast, H-2 I-Ab [B10, B10.A(5R), B6], H-2 I-Ab/k [(B10.A x B10)F1 and (B10 x B10.A)F1], and H-2 I-Abm12 (bm12) mice were resistant against T-cell lymphomagenesis, but 65% of these H-2 I-Ab, b/k, bm12 animals developed B-cell lymphomas (mean latency, 71 weeks). Animals of T-cell lymphoma-susceptible strains that escaped from T-cell lymphomagenesis developed B-cell lymphomas with similar frequency as animals of T-cell lymphoma-resistant strains, but with a shorter latency. H-2 class II-determined regulation of antiviral immunity was reflected in the presence of high titers of antiviral envelope antibodies in T-cell lymphoma-resistant B-cell lymphoma-susceptible H-2 I-Ab, b/k, bm12 mice, whereas in T-cell lymphoma-susceptible H-2 I-Ak,d mice no antiviral antibodies were found. At week 4 after neonatal MCF 1233 infection, a high percentage of thymocytes were virally infected in both T-cell lymphoma-susceptible and -resistant mice. However, T-cell lymphoma-resistant animals cleared the thymic infection between weeks 4 and 10 of age, coinciding with a sharp rise in serum levels of antiviral antibodies. We conclude that the pleiotropic effects of MCF 1233 infection in H-2-congenic mice result from MHC class II I-A-determined T-cell response differences.
 ...
PMID:Major histocompatibility complex class II-regulated immunity to murine leukemia virus protects against early T- but not late B-cell lymphomas. 284 68

Cytogenetic studies of B-cell lymphomas have shown a t(14;18) chromosomal translocation in the majority of cases. However, its detection is not always simple to achieve and a new approach is urgently required. Recently, molecular biological analysis has revealed rearrangements of IgH and/or bcl-2 genes in the DNA of lymphomas. In these cases, a translocation-specific fragment, MBR (bcl-2/JH), could be amplified by PCR. Our present study clearly demonstrated the presence of MBR PCR products in 7 out of 8 cases with B-cell lymphoma. Thus, the results indicate that amplification of MBR by PCR is useful for detection of a translocation and therefore clinical diagnosis of lymphoma cells.
 ...
PMID:[Detection of a 14;18 breakpoint cluster region in B-cell lymphomas by PCR methods]. 796 25

Translocation t(14; 18) has been observed in 50-85% of follicular and in 30% of diffuse non-Hodgkin lymphomas. About half of follicle center lymphoma (FCL) undergo histological conversion at relapse to more aggressive diffuse large B-cell lymphoma (DLBCL). This report correlates the molecular bcl-2/IgH rearrangement by PCR and Bcl-2 immunohistochemical (IHC) expression in a series of high grade DLBCLs with and without FCL remnant. Twenty-three paraffin-embedded lymph nodes from DLBCL patients were analyzed. Eleven patients showed FCL remnant (Group A) and 12, did not (Group B). Single PCR from paraffin extracted DNA followed by Southern transfer of products, hybridisation with internal oligoprobes for the MBR/JH and MCR/JH bcl-2 rearrangements and IHC analysis of Bcl-2 expression, were performed. PCR analysis was positive in 34.8% of patients. Bcl-2/IgH gene rearrangements were observed in 8 (34%) cases and 7 (30%) showed Bcl-2 expression on large noncleaved B-cells (centroblasts). 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. Group B patients showed a clear correlation between PCR and IHC studies. Our results suggest a similar frequency of t(14; 18) in DLBCLs to that reported in Europe and USA series. The discordance observed between PCR and IHC, particularly in Group A, points out the necessity to perform both studies in order to detect bcl-2 gene involvement in DLBCLs.
 ...
PMID:Bcl-2 molecular analysis in paraffin-embedded biopsies from diffuse large B-cell lymphomas. 1105 Aug 5

An association between chronic hepatitis C virus (HCV) infection and clonal proliferation of B cells, including B cell lymphoma, has recently been demonstrated. However, the mechanism of malignant transformation is still unknown. It has been shown that B cells from patients with type II mixed cryoglobulinaemia (MC), strongly express the antiapoptotic bcl-2 oncogene product. Therefore, we investigated a possible mechanism of lymphomagenesis, the occurrence of bcl-2 and immunoglobulin gene rearrangement (IgH) in HCV-infected patients. Three groups of patients were studied: (1) 44 patients with HCV and MC (anti-HCV and HCV RNA positive); (2) 59 patients with chronic HCV infection without MC; (3) 50 patients with chronic liver disease (CLD) not related to HCV infection. The t(14;18) translocation (MBR bcl-2-JH) and IgH rearrangement (FR3/JH) were detected by polymerase chain reaction (PCR) in peripheral mononuclear cells. bcl-2 translocation was detected in 17/44 (39%), 7/59 (12%) and in none of the patients of groups 1, 2 and 3 respectively (P < 0.01). Monoclonal IgH rearrangement was detected in 15/44 (34%), 5/59 (8.5%) and 2/50 (4%) patients of groups 1, 2 and 3 respectively (P < 0.05). HCV-infected patients had a higher prevalence of monoclonal IgH rearrangement and bcl-2 translocation than patients with CLD of other aetiologies. These data suggest that HCV may play a role in the multistep mechanism of lymphomagenesis by inducing clonal proliferation of B cells and inhibition of apoptosis.
 ...
PMID:bcl-2 and immunoglobulin gene rearrangement in patients with hepatitis C virus infection. 1116 30

The mechanism of lymphomagenesis of hepatitis C virus (HCV)-related B-cell lymphoma is unknown. Recently, it has been suggested that HCV may induce B-cell clonal proliferation and t(14;18) translocation in patients chronically infected with the virus. Thus, this study investigated the effect of antiviral treatment on immunoglobulin heavy-chain gene (IgH) rearrangement and t(14;18) translocation in HCV infected patients. Twenty-nine patients with chronic HCV infection were studied in whom IgH rearrangement and/or t(14;18) translocation were previously detected. The IgH rearrangement (FR3/JH) and t(14;18) translocation (MBR bcl2-JH) were detected in peripheral blood mononuclear cells by polymerase chain reaction. Fifteen of 29 patients (8 with IgH rearrangement, 6 with t(14;18) translocation, and 1 with both) were treated with either interferon-alpha or by combination therapy with interferon and ribavirin for 6 to 12 months. IgH rearrangement became negative in 7 of 9 treated patients compared with only 1 of 8 of nontreated patients (P <.02). The t(14;18) translocation became negative in 6 of 7 treated patients compared with 1 of 6 nontreated patients (P =.03). Disappearance of IgH rearrangement or t(14;18) translocation was strongly associated with virologic response to treatment. Two t(14;18)+ patients developed B-cell lymphoma during follow-up. Antiviral treatment appears to be effective in eliminating the clonal proliferation of B cells in patients with chronic HCV infection and may prevent the subsequent development of lymphoma. The mechanism can be related to a direct effect of interferon-alpha on the proliferating clone or to an indirect effect by eradicating the antigenic stimulus.
 ...
PMID:The effect of antiviral therapy on t(14;18) translocation and immunoglobulin gene rearrangement in patients with chronic hepatitis C virus infection. 1123 90

We report the clinical, cytogenetic, fluorescence in situ hybridization (FISH) and molecular findings in a 54-yr-old male patient diagnosed with B-cell chronic lymphocytic leukemia (B-CLL), who showed progression to a diffuse large B-cell lymphoma (Richter's syndrome). Genetic studies were performed at diagnosis and during the Richter's transformation (RT). A clonal karyotype with two dicentric chromosomes, psu dic(12,21)(q24;q10) and dic(17,18)(p11.2;p11.2), was found. Both rearrangements were confirmed by FISH. Molecular cytogenetics analysis using p53 probe showed monoallelic loss of this tumor suppressor gene in 43.8% and 77.3% of cells for the first and the second studies, respectively). In both studies, deletions of D13S319 (18% and 12% of cells) and D13S25 loci (13% and 12% of cells) at 13q14 were found. Polymerase chain reaction analysis showed the MBR/JH rearrangement of the bcl-2 gene. FISH studies using LSI bcl-2/IgH probe allowed quantifying the clonal cell population with this rearrangement (4% and 6.6% of cells at diagnosis and RT, respectively). To our knowledge, this is the first case with a psu dic(12,21) described in B-CLL. The low percentage of cells with the 13q14 deletion and bcl-2/IgH rearrangement suggests that they were secondary events that resulted from clonal evolution. Our patient had a short survival (9 months) and a clear lack of response to several therapeutic agents, confirming the association of p53 gene deletion and karyotypic evolution with disease progression.
 ...
PMID:Cytogenetic, FISH, and molecular studies in a case of B-cell chronic lymphocytic leukemia with karyotypic evolution. 1246 Feb 36

Rituximab is a monoclonal antibody against the CD20 molecule which is used to treat B-cell lymphomas. In 60% of low-grade B lymphomas in which rituximab was effective at first, there was no clinical response in a second treatment and a few cases of follicular lymphomas (FL) with transformation to diffuse large B-cell lymphoma (DLBCL) have been reported. We describe a new case and hypothesize about the mechanisms of transformation: a 52-year-old man, in follow-up during 8 years for FL, who after rituximab treatment and complete remission of FL showed progressive disease involving the liver and duodenal mucosa. Immunohistochemical and molecular studies were performed on paraffin-embedded tissue samples of lymph nodes, the small intestine, and liver tumors. After rituximab treatment, biopsies of a liver lesion and the small bowel both showed CD20-negative large B-cell lymphoma. Molecular study of the initial and relapse specimens shows a CDR2 IgH rearrangement with the same height and t14;18 (MBR). The rapid relapse with the same rearrangement of IgH seems to support the interpretation that the change of grade of lymphoma and loss of CD20 expression occurred before rituximab treatment. The existence of a varying proportion of a CD20-negative cell population in every B-cell lymphoma which does not respond to rituximab should therefore be considered. The reduction of CD20 expression could be a resistance mechanism to rituximab retreatment in DLBCL as a consequence of the progression of low-grade B-cell non-Hodgkin's lymphoma (B-NHL). It is necessary to perform new biopsies to evaluate CD20 expression in relapse or the progression of B-cell lymphoma after rituximab treatment.
 ...
PMID:CD20-negative DLBCL transformation after rituximab treatment in follicular lymphoma: a new case report and review of the literature. 1289 84

Telomeres are essential for maintaining chromosomal integrity and stability. We studied here telomere length (TL) in bone marrow and/or lymph node from 36 patients: 29 with follicular lymphoma (FL) at diagnosis and 7 with diffuse large B cell lymphoma secondary to FL (S-DLBCL). TL was evaluated using terminal restriction fragments (TRF) assay. BCL-2 gene rearrangement was analyzed by nested and long distance PCR. Mean TRF values showed significant telomere shortening in FL (4.18 +/- 0.18 Kb) and S-DLBCL (3.31 +/- 0.25 Kb) respect to controls (8.50 +/- 0.50 Kb) (p<0.001). Differences between both histological subtypes (p=0.036) were also detected. Moreover, the samples positive for BCL-2 rearrangements showed longer TL (4.25 +/- 0.19 Kb) than the negative ones (3.39 +/- 0.30 Kb) (p=0.023). A trend to telomere shortening was observed when Major Breakpoint Region (MBR-JH), minor cluster region (mcr-JH) and BCL-2 negative patients were compared (4.35 +/- 0.21 Kb; 3.84 +/- 0.45 Kb and 3.39 +/- 0.30 Kb, respectively). Our results show a TL reduction in FL and S-DLBCL, with significant short TRFs in the last group, suggesting the participation of telomere shortening in tumor progression. Furthermore, the differences detected between BCL-2 positive and negative FL support the involvement of diverse pathogenic mechanisms.
 ...
PMID:[Molecular analysis of telomere length in follicular lymphomas. Its participation in tumor progression]. 1607 9