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

Immunoglobulin gene rearrangements in B-cell lymphoma subtypes may not always be detected by PCR if only one primer set is applied. We therefore analysed a range of low and high grade B-cell lymphoma subtypes for monoclonality using PCR, to determine appropriate primer selection strategies for routine diagnostic use. Semi-nested PCR was performed on 70 unequivocal B-cell lymphoma cases using paraffin-embedded tissue (PET). Consensus primers directed at the framework 3 (Fr3) and framework 2 (Fr2) regions of the immunoglobulin heavy chain (IgH) gene were used to detect monoclonality. Monoclonality was found in 77% of cases using primer Fr3, 58% using Fr2, and in 93% of cases when data were combined for both primers. In 89% of the 38 low grade and 97% of the 31 high grade B-cell lymphomas monoclonality could be detected when combining both primers. Fr3 gave superior results in most of the lymphoma subtypes analysed. We conclude that both Fr3 and Fr2 are useful, in a routine histopathology laboratory, for detecting monoclonality in most B-cell lymphoma subtypes. Certain subtypes, however, are sometimes not targeted by these primers and therefore require additional analyses.
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PMID:Analysis of low and high grade B-cell lymphoma subtypes using semi-nested PCR and two primer sets. 931 Jan 20

De novo CD5-positive (CD5+) diffuse large B-cell lymphoma (DLBL) has recently been identified as constituting a homogeneous subgroup with distinct clinicopathologic and genotypic characteristics, but its origin remains to be elucidated. Previous studies by sequence analysis of the variable region of the immunoglobulin heavy chain (VH) have shown that CD5+ B-cell malignancies such as mantle cell lymphoma (MCL) and B-cell chronic lymphocytic leukemia (B-CLL) cells represent pre-germinal center (pre-GC) stage B cells in contrast with the post-GC stage of most DLBLs, which show somatic hypermutations in VH genes. In the present study, we investigated the VH sequence of de novo CD5+ DLBL to clarify whether CD5+ DLBL represents the pre-GC stage, as do other CD5+ B-cell malignancies, or the post-GC stage, as is typical of DLBL. All eight cases (four CD5+ DLBL and four CD5-negative (CD5-) DLBL) examined by us showed somatic hypermutations in the VH segment and two of the CD5- DLBL cases showed intra-clonal diversity, suggesting that CD5+ DLBLs were derived from the same maturation stage as CD5- DLBL, but were distinct from the other indolent CD5+ B-cell lymphomas of B-CLL and MCL. These data suggest that de novo CD5+ DLBLs do not merely lie within a continuous spectrum with B-CLL and MCL, but represent a biologically distinct variant within the diagnostic framework of diffuse large B-cell lymphoma.
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PMID:Somatic hypermutations in the VH segment of immunoglobulin genes of CD5-positive diffuse large B-cell lymphomas. 943 84

High-grade mucosa-associated lymphoid tissue (MALT) B-cell lymphoma of the stomach shares several features with its low-grade counterpart. The latter is nearly invariably associated with Helicobacter pylori, and the tumor cells of all MALT lymphomas normally express surface antigen receptors; thus, it is possible that the high-grade type, like the low-grade type, is still influenced by interaction with antigen. In the present study, we analyzed the immunoglobulin heavy chain variable (V)-region genes from eight cases of high-grade MALT lymphoma and one case of Burkitt's lymphoma of the stomach. The V-region genes revealed somatic mutations in all cases, leading to the conclusion that high-grade MALT lymphomas derive from antigen-experienced (post-) germinal center B-cells. Nonrandom distribution of replacement and silent mutations within the gene segments in seven of the eight MALT lymphomas indicated that these V-region genes were selected by antigen, at least for some period of time. Five of the cases showed an unusual mutation pattern that was suggestive of selection by autoantigen or superantigen rather than heterogeneous antigen. Analysis for intraclonal variations revealed evidence of ongoing mutations in two cases. In these cases, the tumor clones probably derived from cells affected by a germinal center B-cell reaction, as the microenvironment of the germinal center is required for maintenance of an active hypermutation mechanism. On the other hand, in another two cases, no evidence of intraclonal variations was found. Thus, either these tumor clones were derived from postgerminal center B-cells, or the hypermutation mechanism in the germinal center ceased after some period of time. Given the mutation pattern, it is possible that high-grade MALT lymphomas emerge from further transformation of low-grade MALT lymphomas with accumulation of additional mutations in the complementarity-determining regions.
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PMID:Immunoglobulin VH genes of high-grade mucosa-associated lymphoid tissue lymphomas show a high load of somatic mutations and evidence of antigen-dependent affinity maturation. 952 Sep 41

(NZB x NZW)F1 female (BW) mice spontaneously develop an autoimmune disease, characterized by the production of autoantibodies (autoAbs) and glomerulonephritis, which can be delayed by neutralizing IFN-gamma Abs and accelerated by IFN-gamma injections. To define the role of IFN-gamma in the pathogenesis of glomerulonephritis, we established a population of BW mice deficient in IFN-gammaR (BWgammaR[-/-]) by repeated crossing; these mice were compared with BWgammaR(+/+) and +/- littermates. Of the BWgammaR(+/+) and +/- mice, 50% showed immune complex glomerulonephritis with heavy proteinuria at 8 mo of age, while only 10% of the BWgammaR(-/-) mice were affected at 14 mo. The serum concentration of anti-dsDNA and anti-histone Abs was dramatically reduced in BWgammaR(-/-) mice. The role of IFN-gamma in promoting class switch to IgG2a and IgG3 could not fully account for the impaired production of anti-dsDNA in BWgammaR(-/-) animals since, IgM and IgG1 levels were also reduced. There was a high incidence of B cell lymphoma in the BWgammaR(-/-) mice, which might be related to the suppression of autoAb production. Thus, the absence of glomerulonephritis in BWgammaR(-/-) mice is likely due to a dramatic yet unexplained effect of the inactivation of IFN-gamma signaling on autoAb production.
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PMID:IFN-gamma receptor deletion prevents autoantibody production and glomerulonephritis in lupus-prone (NZB x NZW)F1 mice. 955 72

The majority of thymic lymphomas are either lymphoblastic lymphoma, large B cell lymphoma or Hodgkin's disease, and other types of non-Hodgkin lymphoma are rare. A case of low-grade B cell lymphoma of mucosa-associated lymphoid tissue (MALT) in the thymus is reported. A 55-year-old Japanese female with a history of rheumatoid arthritis (RA) complained of back pain. A mediastinal tumor was identified by computerized tomography and magnetic resonance imaging, and the thymus was resected through median sternotomy. The solid and nodular tumor had several small satellite extensions and was completely confined to within the thymus. Histologically, monotonous medium-sized centrocyte-like cells occupied the medulla of the thymus and infiltrated Hassall's corpuscles (lymphoepithelial lesions). Immunohistochemically, tumor cells were positive for CD20 and CD79a. IgA and kappa light chain restriction were also found in plasmacytoid cells in the tumor. Clonal rearrangement of the immunoglobulin heavy chain gene was demonstrated by polymerase chain reaction. This case was diagnosed as MALT-type low-grade B cell lymphoma in the thymus. This is the first report of low-grade B cell lymphoma in the thymus associated with RA. As autoimmune diseases are known to be associated with lymphoid neoplasms, it is suggested that the RA played an important role in the development of malignant lymphoma in this case.
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PMID:Low-grade B cell lymphoma of mucosa-associated lymphoid tissue in the thymus of a patient with rheumatoid arthritis. 958 69

t(9;14)(p13;q32), a subtype of 14q32 translocation, plays an essential role in the development of lymphoplasmacytoid lymphoma. t(9;14)(p13;q32) Causes juxtaposition of the PAX-5 gene on 9p13 and the IgH gene on 14q32, leading to the deregulation of the PAX-5 gene. We report a case of primary splenic lymphoma with a t(9;14). The histological diagnosis was diffuse large B-cell lymphoma without plasmacytoid differentiation. The lymphoma cells showed a complex karyotype including a t(9;14). Southern blot analysis localized the breakpoint of the PAX-5 gene within a couple of kb regions upstream of the exon 1A, although the involvement of the PAX-5 gene with the immunoglobulin heavy chain gene could not be confirmed.
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PMID:A case of primary splenic large cell lymphoma with a t(9;14)(p13;q32). 963 87

Intravascular large cell lymphoma (malignant angioendotheliomatosis) is a rare, multifocal, intravascular neoplasm of lymphoid cells that preferentially involves the vasculature of the skin and central nervous system. We describe a 54-year-old man with asymptomatic purpuric patches on the lower extremities for 10 years duration and a more recent lesion on the right arm. A biopsy specimen showed intravascular collections of tumor cells with irregular nuclear contours and prominent nucleoli. These cells were leukocyte common antigen (CD45), CD20, and CDW75 positive, but CD3, CD43, CD45RO, and cytokeratin negative. Polymerase chain reaction analysis of the skin for immunoglobulin heavy chain gene rearrangement detected a clonal population of B cells, supporting the diagnosis of a B-cell lymphoma. Peripheral blood showed no abnormal circulating cells. This case of malignant angioendotheliomatosis is unusual for its prolonged clinical course and presence of purpuric patches.
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PMID:Intravascular large cell lymphoma: a patient with asymptomatic purpuric patches and a chronic clinical course. 970 43

The PAX5 gene encodes the BSAP (B-cell-specific activator protein) which is a key regulator of B-cell development and differentiation. A recurring translocation t(9;14)(p13;q32) in non-Hodgkin's lymphoma moves the PAX5 on 9p13 within close proximity of the immunoglobulin heavy chain gene (IGH). KIS-1 cell line was established from a patient with diffuse large cell lymphoma of B-cell type carrying t(9;14). We analysed PAX5/BSAP expression by Northern and Western blotting in a panel of haematological tumour cell lines with other chromosome abnormalities in comparison with that of KIS-1. PAX5 mRNA and BSAP expression were detected in all B-cell lines tested, and the high level in KIS-1 was confirmed. However, a diffuse large B-cell lymphoma cell line and an acute B-lymphoid/myeloid leukaemia cell line expressed the PAX5/BSAP at levels comparable with KIS-1. PAX5 transcripts were readily detectable in clinical materials with a wide variety of B-cell neoplasms by reverse transcriptase-mediated polymerase chain reaction (PCR). Thus, PAX5/BSAP activation in haematological tumour cells is not necessarily associated with t(9;14). Although binding sites for BSAP have been identified in the promoters of CD19, this study failed to find clear correlation between the level of PAX5/BSAP expression and that of CD19. In contrast to KIS-1 in which the E mu enhancer of IGH was juxtaposed to PAX5, cloning of t(9; 14) from another case by long-distance PCR revealed that the PAX5 promoter was linked to a Cgamma constant region in divergent orientation, suggesting that the mechanism of PAX5 activation through recombination with IGH varies among individual cases. Breakpoints on 9p13 of the two translocations were clustered upstream of PAX5, leaving the PAX5 coding region intact.
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PMID:Expression of the PAX5/BSAP transcription factor in haematological tumour cells and further molecular characterization of the t(9;14)(p13;q32) translocation in B-cell non-Hodgkin's lymphoma. 972 95

Antibody (Ab)-based tumor therapeutics use the tumor-binding specificity of the Ab to target Fc functions or associated molecules to the site of the tumor. We have used an Ab-interleukin-2 (IL-2) fusion protein to deliver IL-2 to a murine B cell lymphoma (38C13). This anti-Id IgG3-CH3-IL-2, which recognizes the idiotype present on the surface of the lymphoma has a half-life in mice approximately 17-fold longer than the half-life reported for IL-2. Gamma camera studies showed that anti-Id IgG3-CH3-IL-2 localizes at the site of a subcutaneous tumor in mice. The anti-Id IgG3-CH3-IL-2 also shows enhanced antitumor activity compared with the combination of Ab and IL-2 administered together. However, the mechanism of antitumor activity appears to depend on the dose and the treatment schedule used. A single dose of fusion protein prevented tumor in only 50% of the animals, although all the survivors showed some evidence of immunologic memory. Although multiple doses are more effective in preventing tumor growth (87% survivors), they are ineffective in generating protective immunologic memory. Our results suggest that Ab-IL-2 fusion proteins will be useful in the diagnosis and treatment of human B cell lymphomas and other related malignancies.
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PMID:An IgG3-IL-2 fusion protein recognizing a murine B cell lymphoma exhibits effective tumor imaging and antitumor activity. 972 41

A close relationship between Hashimoto thyroiditis (HT) and low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) has been shown. We used immunohistochemistry to study paraffin sections from 40 unselected cases of HT and scored cases according to the lymphoid infiltrate and presence of lymphoepithelial lesions (LELs). Clonality was assessed by kappa/lambda immunohistochemistry and polymerase chain reaction for immunoglobulin heavy chain gene rearrangement (IgH PCR). Histologic findings were compared with 2 cases of primary thyroid MALT-type lymphoma. In HT, the lymphoid infiltrate consisted predominantly of T cells in all cases; B cells, associated with germinal centers, did not have the appearance of marginal zone cells. All cases had identifiable T-cell LELs; immunohistochemistry confirmed inconspicuous, rare B-cell LELs in 13 of 40 cases. In all cases, plasma cells were polyclonal and IgH PCR showed a polyclonal pattern. Clinical follow-up was available for 34 patients. Lymphoma developed in none. In contrast, a B-cell predominant infiltrate of marginal zone cells was present in the MALT-type lymphomas that was not confined to germinal centers. Cytokeratin stains demonstrated severe loss of epithelial elements and destructive LELs. LELs are not, in isolation, a useful criterion for distinguishing low-grade MALT-type lymphoma of the thyroid from HT. Features associated with low-grade MALT-type lymphoma include a predominance of B cells, marked loss of epithelial elements, and destructive LELs composed of marginal zone B cells. Unselected cases of HT do not contain monoclones detectable by IgH PCR.
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PMID:Characterization of the lymphoid infiltrate in Hashimoto thyroiditis by immunohistochemistry and polymerase chain reaction for immunoglobulin heavy chain gene rearrangement. 972 7


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