Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Testicular lymphomas usually occur in older men and are mostly diffuse large B-cell lymphomas (DLBL). They may be primary manifestation of lymphoma or represent a relapse of a previous non-Hodgkin's lymphoma. This report details a testicular large cell lymphoma, which was proven to be large cell transformation of a low-grade follicular lymphoma biopsied 8 years earlier. Initially, a 38-year old man was diagnosed with cervical lymphadenopathy, and biopsy was interpreted as reactive follicular hyperplasia; no treatment was given, and the lymphadenopathy resolved spontaneously. Eight years later, the patient underwent surgery for a left testicular mass and gastroscopy for gastric symptoms. The patient died 7 months later with evidence for intra-abdominal and central nervous system lymphoma after a brief but temporary response to M-BACOD chemotherapy. Orchiectomy specimen and gastroscopic biopsy showed diffuse large B-cell lymphoma (CD20+), which infiltrated between well-preserved tubules in the testis. Histological comparison with 20 testicular lymphomas without previous lymphoma showed tubule infiltration in all cases, suggesting that the tubule-preserving infiltration pattern could be a histological marker for secondary lymphoma involvement in testis. On re-examination, the lymph node 8 years prior was verified as follicular, predominantly small, cleaved cell lymphoma with bcl2-positive follicles. The earlier follicular lymphoma and the subsequent diffuse large cell lymphoma were analyzed using polymerase chain reaction and showed identical sequences of the t(14;18) translocation and immunoglobulin heavy chain gene rearrangement. Analysis of the VH-gene sequences from the follicular lymphoma revealed sequence heterogeneity consistent with ongoing mutation. However, the transformed diffuse large cell lymphoma had no intraclonal variation, with the sequence matching with one of the subclones from the low-grade follicular lymphoma. These results confirm that the large cell transformation of follicular lymphoma occurs in a single follicular lymphoma cell. This case also indicates that the selection of the transformed clone can be part of the natural history of disease and can occur without exposure to chemotherapy.
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PMID:Testicular diffuse large cell lymphoma with tubule preservation--molecular genetic evidence of transformation from previous follicular lymphoma. 1078 87

The Bcl-2 family of proteins play a prominent role in the regulation of apoptosis. From the initial identification of bcl-2 as an oncogene in follicular lymphoma through genetic studies in Caenorhabditis elegans to recent functional studies focusing on the importance of mitochondrial events in cell death signalling, the members of this protein family continue to be implicated in pivotal decision points regarding the survival of the cell. The family can be divided into two classes: those such as Bcl-2 and Bcl-xL that suppress cell death, and others, such as Bak and Bax, that appear to promote apoptosis. The Bcl-2 family is characterized by specific regions of homology termed Bcl-2 homology (BH1, BH2, BH3, BH4) domains, which are critical to the function of these proteins, including their impact on cell survival and their ability to interact with other family members and regulatory proteins. The identification of the BH3 domain as a potent mediator of cell death has led to the emergence of an additional family of proapoptotic proteins (such as Bad, Bik, Bid and Hrk) that share identity with Bcl-2 only within this death domain. These BH3-only proteins may be part of a regulatory network serving to integrate cell survival and death signals, an assertion that is supported by the identification of a BH3-only protein, Egl-1, as part of the central core of cell death signalling in C. elegans. While the mechanism of action of the BH3-only proteins remains unclear, recent studies on the regulation of critical protein-protein interactions and activity of Bad by phosphorylation in response to growth factor signalling suggest that the active state of BH3-only proteins may be regulated by post-translational modification. Additional modes of regulation, such as transcriptional, translational and subcellular localization, are also likely to be important.
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PMID:Role of the BH3 (Bcl-2 homology 3) domain in the regulation of apoptosis and Bcl-2-related proteins. 1081 98

Follicular lymphoma (FL) cells express CD20 and are associated in most cases with the t(14;18) chromosomal translocation. A multicentre study was undertaken between January 1997 and January 1998 to assess the complete response rate (CR) and overall response rate (RR) to rituximab, a chimaeric anti-CD20 monoclonal antibody. Seventy patients with previously treated FL received rituximab (375 mg/m2/week x4, by intravenous infusion). Restaging studies were performed 1 and 2 months after therapy. Molecular monitoring for the presence of cells harbouring the Bcl-2/JH gene rearrangement in the peripheral blood (PB) and bone marrow (BM) was performed before and after treatment using a two-step semi-nested polymerase chain reaction (PCR) assay. The overall RR was 32/70 (46%), being highest in patients who had received only one previous treatment (12/15, 80%). However, only two patients achieved a CR. The median duration of response was 11 months. Thirteen of 21 evaluable 'PCR-positive' patients (62%) became 'PCR-negative' in PB and/or BM samples 1 month after rituximab, although this did not correlate with clinical response. Treatment was generally well tolerated, although one patient developed Stevens-Johnson syndrome. Rituximab was shown to be active in FL, and in some cases PB and/or BM became PCR negative. Studies in combination with cytotoxic chemotherapy to increase the CR rate are warranted.
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PMID:A UK multicentre phase II study of rituximab (chimaeric anti-CD20 monoclonal antibody) in patients with follicular lymphoma, with PCR monitoring of molecular response. 1084 85

This report summarizes a cumulative 4-year experience in polymerase chain reaction (PCR) analysis of immunoglobin heavy chain (IgH) and TcR-gamma chain gene rearrangements in 525 cases of lymphoproliferative disorders. Because the sensitivity of the PCR methodology was found to be tissue dependent, in the study of the presence of clonal cell population in tissues containing a small number of polyclonal lymphocytes, such as skin and gastrointestinal biopsy specimens, we used the multiple-PCR run approach. In this latter methodology, we repeat the PCR reaction from the same sample at least three times to confirm the reproducibility of the results. In the study of 273 cases of B- or T-cell lymphomas with characteristic immunomorphological and clinical features, a clonal IgH or TcR-gamma chain gene rearrangement was detected in approximately 80% of cases. A clonal rearrangement involving both IgH and TcR-gamma chain genes was found in 10% of cases of both B-cell and T-cell lymphomas. The study of 167 cases of nonneoplastic lymphoid tissue samples showed the presence of clonally rearranged cell populations for IgH or TcR-gamma genes in 3 and 9% of cases, respectively. We also applied PCR for the study of 85 cases of lymphoproliferations with no definite diagnosis (i.e., benign versus malignant) after immunomorphological analysis. In 65 cases (76%), the correlation of immunomorphological features with the presence (48 cases) or the absence (17 cases) of clonal lymphoid cell populations led to a definite diagnosis. In almost all these cases, the final diagnosis was found to be in agreement with the clinical course. In the 20 remaining cases (24%), no definite diagnosis could be made. We also assessed the value of PCR in detecting bcl-2/J(H) gene rearrangement as an additional clonal marker in the diagnosis of follicular lymphoma. Bcl-2/J(H) rearrangement and/or IgH gene rearrangement was found in approximately 85% (71/85) of follicular lymphoma cases studied.
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PMID:PCR analysis of immunoglobulin heavy chain (IgH) and TcR-gamma chain gene rearrangements in the diagnosis of lymphoproliferative disorders: results of a study of 525 cases. 1114 22

Follicular lymphoma is the most common low-grade B-cell lymphoma. It is characterized by at least a partial follicular growth pattern in the majority of cases, by the morphological resemblance of the tumour cells to follicle centre centroblasts and centrocytes, and by the distinctive expression of Bcl-2 protein as a consequence of a translocation between chromosomes 14 and 18, resulting in the juxtaposition of Bcl-2 and the immunoglobulin heavy chain locus. It is not known whether the follicular growth pattern of follicular lymphoma is a consequence of properties of the tumour cells, or whether the tumour cells invade and gradually occupy a niche generated by a normal T-cell-dependent B-cell response. This study has identified cases of follicular lymphoma in which the tumour cells are apparent within a normal reactive germinal centre background. The reactive background has been investigated in these cases and also in cases showing a more characteristic appearance, in which entire malignant follicles appear to be Bcl-2-positive, as assessed by microdissection and analysis of clonality by the polymerase chain reaction (PCR). A reactive oligoclonal background was observed in all cases studied, characteristic of a normal follicle centre response. These data suggest that the progression of follicular lymphoma is dependent on the normal germinal centre microenvironment. Disruption of this dependence might be considered as a novel therapeutic strategy.
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PMID:Relative distribution of tumour cells and reactive cells in follicular lymphoma. 1127 9

The t(14;18) translocation is a useful marker to characterize follicular lymphoma and to monitor residual disease. The polymerase chain reaction (PCR) is a powerful technique to detect this translocation. Located on chromosome 18, within the Bcl-2 gene, breakpoints occur mainly in the 3; untranslated region, in the third exon of Bcl-2 (MBR region). In this study, the authors amplified MBR breakpoints by PCR and found an unexpectedly large fragment of 1 Kb that corresponds to a recently described new breakpoint in the Bcl-2 gene. With a new primer set, a further previously considered t(14;18)-unrelated tumor was in fact positive for this new breakpoint.
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PMID:A 1-kb Bcl-2-PCR fragment detection in a patient with follicular lymphoma and development of a new diagnostic PCR method. 1138 16

The lack of precise and homogeneous criteria for the recognition of primary cutaneous follicular lymphoma has hindered gaining data on the frequency and clinical and molecular features of this entity. In the course of a review of a series of primary cutaneous lymphoma from different Spanish hospitals, we collected a series of 18 cases of primary cutaneous follicular lymphoma and analyzed its clinical, morphologic, and biologic characteristics. In this review only cases with a follicular pattern of growth, germinal center cytology, and restriction to the skin in a minimum follow-up of 6 months have been included. Cases of primary cutaneous follicular lymphoma were characterized by the expression of classic markers of the germinal center, such as bcl6, CD10, and the presence of aggregates of follicular dendritic cells. They frequently express bcl2 protein, although classical t(14;18) was not found in any of the cases analyzed. Analysis of the bcl6 noncoding first exon showed somatic mutations in two of four cases analyzed, as would be expected in lymphoma deriving from the germinal center. Clinically, most cases showed initial involvement of the head and neck, with relapses in eight cases (involving the skin in five cases, both skin and lymph node in two cases, and lymph node in one case). No death attributable to the tumor was recorded. These data seem to imply that follicular lymphoma may present initially in the skin, lacking the characteristic t(14;18) and having a relatively indolent course. Recognition of these tumors and elucidation of their molecular alterations could lead to properly adapted staging and treatment protocols for these patients.
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PMID:Cutaneous follicular B-cell lymphoma: description of a series of 18 cases. 1142 Apr 58

A synergistic interaction of Bcl-2 and c-Myc plays a role in lymphomagenesis in mice and in some patients as well. Progression of follicular lymphoma to a more aggressive lymphoma is seen in the majority of patients, and approximately 10% of the transformed lymphomas have a translocation of c-myc in addition to the translocation of bcl-2 found in the original follicular lymphoma. We investigated whether transcriptional deregulation of bcl-2 and c-myc could be examined in primary lymphoma cells by in vivo footprinting and in vitro protein-DNA binding studies. A matched pair of follicular and transformed lymphoma samples was examined. The transformed lymphoma had acquired a translocation of c-myc into the immunoglobulin heavy chain locus. High levels of bcl-2 expression were observed in both the follicular and transformed lymphomas, whereas the expression of c-myc was low in the follicular lymphoma and increased in the transformed lymphoma. In vivo footprint analysis revealed that a CRE site and a Cdx site in the bcl-2 promoter were occupied on the translocated alleles but not on the normal alleles in both the follicular and transformed lymphomas. Two nuclear factor kappaB sites were occupied on the translocated c-myc allele in the transformed lymphoma. Gel shift analysis revealed that these proteins bound to their respective sites in the bcl-2 or c-myc promoter. There was no evidence that the presence of one of the translocations in the immunoglobulin heavy chain locus influenced the expression of the other translocated gene.
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PMID:Molecular mechanisms of transcriptional control of bcl-2 and c-myc in follicular and transformed lymphoma. 1143 60

The description of primary cutaneous follicular lymphoma has raised interest in the differential diagnosis of this versus disseminated follicular lymphoma involving the skin. We report here on four cases of Stage IV follicular lymphoma, diagnosed in skin biopsy, in which cutaneous lesion was the most noticeable feature of clinical presentation. In all cases, the morphological features were superimposed over typical nodal follicular lymphoma. Apart from classic B-cell markers, they were characterized by CD10 and bcl6 positivity, markers of follicle germinal center cells; and bcl2 expression, with a corresponding t(14;18) translocation in three of three cases examined. In all four cases, bone marrow study and clinical staging revealed disease that had disseminated since diagnosis. Follow-up showed relapsing cutaneous and nodal disease in two cases. The only difference observed with a control group of 10 cases of primary cutaneous follicular lymphoma was the absence in this group of t(14; 18). Disseminated classical follicular lymphoma has to be considered in the differential diagnosis of follicular lymphoma presenting in the skin. This series of cases suggests that the presence of t(14;18) could imply the existence of disease that has disseminated beyond the skin and that cases harboring this translocation could be candidates for systemic polychemotherapy.
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PMID:Cutaneous presentation of follicular lymphomas. 1155 89

The exact classification of primary cutaneous follicle center cell lymphomas (FCCLs) has been the subject of ongoing debate. In the classification of cutaneous lymphomas proposed by the European Organization for Research and Treatment of Cancer (EORTC)-Cutaneous Lymphoma Project Group, cutaneous follicle center cell lymphoma (FCCL) is defined as a proliferation of centrocytes and centroblasts showing a diffuse pattern of growth in the great majority of cases, and presenting only rarely a true follicular pattern. CD10 and Bcl-2 are usually not expressed by neoplastic cells, and the t(14:18) is absent. By contrast, nodal follicular lymphoma is a tumor with a follicular pattern, characterized by the proliferation of CD10+, Bcl-2+ follicular cells, and by the presence of the t(14;18) in most cases. In this review we outline the clinicopathologic, phenotypic, and molecular features of primary cutaneous FCCL, reviewing criteria for diagnosis and differential diagnosis of this peculiar variant of cutaneous B-cell lymphoma.
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PMID:Primary cutaneous follicle center cell lymphoma. 1169 44


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