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Query: UMLS:C0079731 (B-cell lymphoma)
 16,671 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The posttransplantation lymphoproliferative disorders (PT-LPDs) are a morphologically heterogeneous group of Epstein-Barr virus (EBV)-driven lymphoid proliferations of varying clonal composition. Some PT-LPDs regress after a reduction in immunosuppression, while others progress in spite of aggressive therapy. Previously defined morphologic categories do not correlate with clonality, and neither morphology nor clonality has reliably predicted the clinical behavior of PT-LPDs. We investigated 28 PT-LPD lesions occurring in 22 patients for activating alterations involving the bcl-1, bcl-2, c-myc, and H-, K- and N-ras proto-oncogenes and for mutations involving the p53 tumor suppressor gene. We correlated the results of these studies with the morphology of the lesions, their clonality based on Ig heavy and light chain gene rearrangement analysis, and the presence and clonality of EBV infection. We found that the PT-LPDs are divisible into three distinct categories as follows: (1) plasmacytic hyperplasia: most commonly arise in the oropharynx or lymph nodes, are nearly always polyclonal, usually contain multiple EBV infection events or only a minor cell population infected by a single form of EBV, and lack oncogene and tumor suppressor gene alterations; (2) polymorphic B-cell hyperplasia and polymorphic B-cell lymphoma: may arise in lymph nodes or various extranodal sites, are nearly always monoclonal, usually contain a single form of EBV, and lack oncogene and tumor suppressor gene alterations; and (3) immunoblastic lymphoma or multiple myeloma: present with widely disseminated disease, are monoclonal, contain a single form of EBV, and contain alterations of one or more oncogene or tumor suppressor genes (N-ras gene codon 61 point mutation, p53 gene mutation, or c-myc gene rearrangement). The PT-LPDs are divisible into three categories exhibiting distinct morphologic and molecular genetic characteristics. Alterations involving the N-ras and c-myc proto-oncogenes and the p53 tumor suppressor gene may play an important role in the development and/or progression of the PT-LPDs.
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PMID:Correlative morphologic and molecular genetic analysis demonstrates three distinct categories of posttransplantation lymphoproliferative disorders. 781 11

Large multilobated cell lymphomas represent an heterogenous group comprising both B-cell and T-cell subtypes. The correct lineage identification of each subtype cannot be based on morphologic grounds, as it has already been stressed by other authors, and demands the use of immunophenotyping methods. In this study we review the literature and present eight new cases of large multilobated B-cell lymphoma which have been immunophenotyped in paraffin sections with a panel of monoclonal [L26 (CD20), 4KB5 (CD45R), UCHL1 (CD45RO), MT1 (CD43)] and polyclonal (anti-CD3, anti-kappa, anti-lambda) antibodies. We further investigated the expression of c-myc p62 oncoprotein and of proliferating cell nuclear antigen (PCNA) using the monoclonal antibodies c-myc 1-9E10 and PC-10 respectively. In all cases the neoplastic cells were positive for L26 (CD20) and negative for anti-CD3. Five cases were positive for 4KB5 (CD45R) while six cases stained positively for UCHL1 (CD45RO) or MT1 (CD43). Four cases were monoclonal in respect to light chain restriction. Immunoreactivity with c-myc 1-9E10 and PC-10 was observed in all cases. As far as c-myc 1-9E10 is concerned, positive cells constituted more than 45% of the neoplastic population in six cases, whereas in all cases the percentage of PC-10 positive cells was greater than 45%. The staining pattern was nuclear and/or cytoplasmic for c-myc 1-9E10 but solely nuclear for PC-10. The elevated c-myc and PCNA expression are indices of high proliferation rate in this type of lymphoma and may suggest a high malignancy grade.
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PMID:B-cell lymphoma of large multilobated type: an immunohistochemical study of 8 cases and review of the literature. 802 16

In a prospective necropsy study involving 257 animals in the BB rat colony in Edinburgh, there was an increased incidence of lymphoma (average 10.9 per cent in all three subgroups: 8 per cent in diabetic, 20 per cent in non-diabetic diabetes-prone, and 3.2 per cent in diabetes-resistant rats). The incidence was significantly increased (P < 0.05) in the non-diabetic diabetes-prone subgroup. These results differ markedly from previous results and indicate that the relationship between lymphoma and diabetes is more complex than previously suggested. All the lymphomas bar one involved the ileocaecal nodes and were classified as immunoblastic lymphomas of B-cell origin. There was a striking resemblance both in tissue distribution and in histological classification to the lymphoma seen in the established B-cell lymphoma model, the LOUVAIN rat. Southern blot analysis carried out on the BB rat lymphomas revealed a translocation of variable length involving the c-myc oncogene. Such a translocation has not been demonstrated in the BB rat before.
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PMID:Lymphoma in the BB/E rat: c-myc translocation identified. 832 62

A conditional mutant of Epstein-Barr virus nuclear antigen 2 (EBNA2) regulated by estrogen was employed to study the effect of EBNA2 on the cellular phenotype. Activation of EBNA2 in lymphoblastoid cell lines (LCLs) and in B cell lymphoma lines resulted in down-regulation of cell surface IgM and Ig-mu steady-state RNA expression. In LCLs, activation of EBNA2 is required for maintaining proliferation, whereas in Burkitt's lymphoma (BL) cell lines with t(8;14) translocations, activation of EBNA2 induces growth arrest. In these cells, Northern and nuclear run-on analyses revealed rapid simultaneous repression of Ig-mu and c-myc transcription as early as 30 min after activation of EBNA2. Since c-myc expression is under the control of the Ig heavy chain locus in BL cell lines with a t(8;14) translocation, we propose that Ig-mu and c-myc are down-regulated by EBNA2 through a common mechanism.
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PMID:Epstein-Barr virus nuclear antigen 2 is a transcriptional suppressor of the immunoglobulin mu gene: implications for the expression of the translocated c-myc gene in Burkitt's lymphoma cells. 861 12

Primary mediastinal B cell lymphoma (PMBL) is a diffuse large B cell lymphoma (DLCL) postulated to arise from noncirculating thymic B lymphocytes. Because of its distinctive clinical and morphological features and putative unique cellular origin, PMBL is generally considered a distinct clinicopathological entity. Little is known, however, about the molecular characteristics of PMBL. Therefore, we analyzed 16 PMBLs for molecular alterations involving the bcl-1, bcl-2, bcl-6, c-myc, H-ras, K-ras, N-ras, and p53 genes and for Epstein-Barr virus infection, which are commonly involved in lymphoid neoplasia. Employing a combination of Southern blotting and/or polymerase chain reaction and single-strand conformation polymorphism assays, we detected genetic alterations in 7 of the 16 (44%) PMBLs. Whereas the bcl-6 gene is rearranged in up to 45% of DLCLs, rearrangement of the bcl-6 gene was detected in only 1 of these 16 (6%) PMBLS. Point mutations of the 5' noncoding region of the c-myc gene were demonstrated in 3 other cases (19%), although c-myc gene rearrangements were not seen by Southern blotting. Missense point mutations of the p53 gene were identified in 3 additional PMBLs (19%). Alterations of the bcl-1, bcl-2, or ras genes and evidence of Epstein-Barr virus infection were not observed. In conclusion, a variety of molecular lesions occur in PMBLs and may be involved in their pathogenesis. This molecular genetic pattern bears little resemblance to that known for other B cell malignancies, including DLCL. In particular, the infrequent occurrence of bcl-6 gene rearrangement in PMBLs distinguishes them from other DLCLs of B cell origin, suggesting that PMBLs do not represent a distinct subtype of DLCL.
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PMID:Molecular characterization of primary mediastinal B cell lymphoma. 866 86

The Epstein-Barr virus (EBV) nuclear antigen-1 (EBNA-1) is a pleiotropic protein which has been characterized extensively both biochemically and functionally. It is the only one of the identified latent protein-encoding genes to be consistently expressed in viral-associated endemic Burkitt's lymphoma cells. As such, it is the only candidate viral protein to possibly perform a maintenance function in the tumour pathology. Despite this, no oncogenic activity has been attributed to the protein in tissue culture assays. The experiments described here were initiated to explore the activity of the protein in B cells in vivo. EBNA-1 transgenic mice were generated with transgene expression directed to the B cell compartment using the mouse Ig heavy chain intron enhancer. Transgene expression was demonstrated in the lymphoid tissues of mice of two independent lines. Transgenic positive mice of both lines succumb to B cell lymphoma. The B cell tumours are monoclonal, frequently of follicular centre cell origin and remarkably similar to those induced by transgenic c-myc expression. These results demonstrate that EBNA-1 is oncogenic in vivo and suggest that the gene product may play a direct role in the pathogenesis of Burkitt's lymphoma and possibly other EBV-associated malignancies.
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PMID:Expression of Epstein-Barr virus nuclear antigen-1 induces B cell neoplasia in transgenic mice. 867 Aug 12

Cytogenetic, in situ hybridization, and molecular studies were performed in a case of T-cell-rich B-cell lymphoma. Demonstration of Ig gene rearrangements for both heavy and light chains confirmed the B-lineage restriction of the neoplastic cell population. Moreover, as expected in B-cell malignancies, all abnormal karyotypes showed a 14q+ chromosome marker involving 14q32. The origin of the extra material on the derivative 14q+, as defined by chromosome painting with a library for chromosome 11, and Southern blotting for c-myc and bcl-2 rearrangements, remains unknown.
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PMID:14q+ chromosome marker in a T-cell-rich B-cell lymphoma. 868 94

A case of CD5-positive diffuse large cell lymphoma in a patient with autoimmune hemolytic anemia (AIHA) is reported. The patient was diagnosed with AIHA in December 1988. Three and a half years later, the patient complained of fever and left sided flank pain. Abnormal lymphocytes appeared in the peripheral blood and were positive for HLA-DR, CD5, CD19, CD20, and surface immunoglobulin (mu, lambda). The pathological diagnosis of the cervical lymphnode was non-Hodgkin lymphoma; diffuse large cell type with a starry sky-like appearance. Although the 8q24 translocation was not detected by karyotypic analysis of the peripheral blood mononuclear cells (PBMNC), Southern blot analysis revealed that the c-myc rearrangements had occurred. This case showed two rearranged bands with Eco RI, Bam HI, or Bgl II digestion, and a germline band with Hin dIII digestion using a second exon fragment of the c-myc gene as a probe. Despite intensive chemotherapy, this patient died 6 months after being diagnosed with malignant lymphoma. We discuss the c-myc rearrangements in this aggressive CD5-positive diffuse large B cell lymphoma.
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PMID:Aggressive CD5-positive diffuse large B cell lymphoma showing c-myc rearrangements developed in a patient with autoimmune hemolytic anemia. 871 79

myc oncogenes are transcription factors regulating the level of expression of other genes. Using a subtraction/coexpression strategy, a murine genetic target for Myc regulation was isolated. To further characterize this target gene, named ECA39, we have recently isolated the human, nematode and budding yeast homologs of the mouse gene. The recognition site for Myc binding, located 3' to the start site of transcription in the mouse gene, is conserved in the human homolog. Transfection experiments demonstrated that the Myc binding site of the human gene, mediates activation of a reporter gene in response to over-expression of c-myc. The activation was better executed when the c-Myc binding element was positioned downstream to the promoter, which is the usual position of the c-Myc DNA binding element in its genetic targets. The tissue specific expression of human ECA39 during embryogenesis is similar to that of the mouse homolog. Moreover, ECA39 is expressed in c-myc induced human tumors. It is expressed in Burkitt's lymphoma (where c-myc is translocated and activated) but not in non Burkitt's B-cell lymphoma or in T-cell lymphoma. Thus, it seems that ECA39 is a target for c-myc oncogenesis in humans. In yeast, where c-myc is absent, the ECA39 sequences lack the c-Myc binding element. However, the promoter region of the yeast ECA39 harbors several Gcn4 binding elements. Moreover, ECA39 is markedly down regulated in cells deleted for gcn4, and deletion of Gcn4 binding elements down regulated the transcription from ECA39 promoter. We thus suggest that ECA39 is a target for c-Myc regulation in mammals, while in yeast the regulator is not c-Myc but the c-Jun/c-Fos homolog - Gcn4.
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PMID:ECA39 is regulated by c-Myc in human and by a Jun/Fos homolog, Gcn4, in yeast. 893 31

The protein product of the proto-oncogene bcl-2, originally discovered by virtue of its chromosomal translocation in human follicular centre B cell lymphoma, is a physiological inhibitor of programmed cell death, apoptosis. Initial studies in transgenic mice overexpressing Bcl-2 in B or T lymphocytes demonstrated that Bcl-2 can potently antagonise cell death induced by multiple independent signal transduction routes and can contribute to oncogenesis, particularly in combination with other oncogenes, like c-myc, that promote cell proliferation. Further investigations using crosses between bcl-2 transgenic mice and T cell receptor or immunoglobulin transgenic mice or mutant mice deficient in proper antigen receptor gene rearrangement demonstrated that Bcl-2 can only block death of cells that failed to receive a positive stimulus, "death by neglect', but not activation induced apoptosis. Collectively, these results provide evidence that distinct signalling pathways for apoptosis converge upon a common effector machinery where Bcl-2 acts as an antagonist, but that there also exists a mechanism that can either bypass the Bcl-2 checkpoint or override its protective function. These experimental data are reviewed here and discussed in context of current knowledge of lymphocyte differentiation, tumorigenesis and cell death regulation.
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PMID:Lessons from bcl-2 transgenic mice for immunology, cancer biology and cell death research. 895 Apr 69


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