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)

Low-grade follicular non-Hodgkin's lymphomas are characterized by the presence of a t(14;18) chromosomal translocation that results in deregulation of the B-cell lymphoma (Bcl-2) gene. Studies in cell lines and transgenic animal models have suggested that this results in the suppression of apoptotic cell death in germinal centers. B lymphocytes from normal germinal centers and lymph nodes infiltrated by follicular lymphoma were isolated by immunomagnetic depletion of cells bearing CD4, CD8, or slgD for study in vitro. Follicular lymphoma cells expressing Bcl-2 protein were shown to resist apoptosis after isolation, and could be induced to proliferate in a culture system previously described for the growth of normal B lymphocytes. By the use of a mouse fibroblast monolayer transfected with the CDw32 Fc receptor to present CD40 monoclonal antibody in the presence of interleukin-4, prolonged culture was possible. Karyotypic analysis of cultured lymphoma cells showed the t(14;18) translocation, with clonal identity confirmed by polymerase chain reaction amplification of the breakpoints and direct sequence analysis. These findings support the hypothesis that resistance to apoptosis is an influence on the initiation of follicular lymphoma, and provide a novel means of studying in vitro the intercellular reactions that may be important in progression of the disease.
 ...
PMID:Isolated follicular lymphoma cells are resistant to apoptosis and can be grown in vitro in the CD40/stromal cell system. 769 Dec 40

The B7/BB1 molecule has recently been found to be expressed on professional antigen-presenting cells and to be the natural ligand for CD28 and CTLA-4 on T cells. On binding of B7/BB1, CD28 transduces a signal that synergizes with triggering of the T-cell antigen receptor, resulting in enhanced cytokine secretion. In view of the data supporting an antigen-presenting function of Reed-Sternberg cells, we evaluated the expression of B7/BB1 in lymph nodes affected by Hodgkin's disease. B7/BB1 was found to be strongly expressed by the Reed-Sternberg cells in all 47 cases of Hodgkin's disease studied. Moreover, Reed-Sternberg cells were frequently surrounded by CD28-expressing T cells. Evidence for a functional role of B7/BB1 on Reed-Sternberg cells was obtained by our findings that T-cell proliferation and interleukin-2 (IL-2) production in the primary allogenic mixed lymphocyte reaction (MLR), using the B7/BB1-expressing Hodgkin's disease-derived cell lines L428 and KM-H2 as stimulators, could be partially blocked by adding anti-B7 monoclonal antibody. B7/BB1 expression was also evaluated in a group of non-Hodgkin's lymphomas (n = 46). Whereas B7/BB1 was not expressed by the neoplastic cells of most non-Hodgkin's lymphomas, including T-cell-rich B-cell lymphoma (n = 11), it was present on the neoplastic cells of anaplastic large-cell lymphoma (Ki-1 lymphoma) (n = 5) and follicular lymphoma (n = 4). Our data provide further evidence for an accessory cell function of Reed-Sternberg cells. The accessory cell function of Reed-Sternberg cells might lead to pronounced T-cell activation in vivo, which might contribute to the Hodgkin's syndrome. In addition, our study indicates that B7/BB1 may be a useful marker for differentiating Hodgkin's disease from morphologically similar conditions such as T-cell-rich B-cell lymphoma.
 ...
PMID:The B7/BB1 antigen is expressed by Reed-Sternberg cells of Hodgkin's disease and contributes to the stimulating capacity of Hodgkin's disease-derived cell lines. 769 51

T-cell-rich B-cell lymphoma (TCRBCL) is a recently described variant of non-Hodgkin's lymphoma. It may arise de novo or secondary to follicular lymphoma and large B-cell lymphoma. We present here seven cases of TCRBCL to emphasize a peculiar relationship to lymphocyte-predominant Hodgkin's disease. Morphologically, the neoplastic populations of all TCRBCLs, in addition to centroblast-like and immunoblast-like cells, comprised a few L+H-like elements. These neoplastic cells were all regularly scattered in a majority of reactive small T-lymphocytes as well as histiocytes. Moreover, tumour cells of TCRBCL, including the L+H-like elements of TCRBCL, expressed LCA and L26 but did not stain for Leu-M1 and BerH2, as is the case with the Reed-Sternberg cell L+H variant of lymphocyte-predominant Hodgkin's disease. Furthermore, the L26 immunoreaction in one of the cases, which otherwise presented as typical TCRBCL, disclosed a small subcapsular area resembling nodular paragranuloma because some few foci consisting of mature B lymphocytes with occasional L+H-like elements were seen. This also holds true for a second of the TCRBCLs presented that obviously coexisted with recurrent Hodgkin's paragranuloma 10 years after the primary manifestation. These findings indicate a close connection between TCRBCL and lymphocyte-rich Hodgkin's disease, and it may even be speculated as to whether TCRBCL represents merely a phenotypically different manifestation of this Hodgkin's subtype. Although the data presented here will not provide sufficient proof of this hypothesis, it seems clear that the nosology of TCRBCL in the context of current lymphoma classifications requires further elucidation.
 ...
PMID:T-cell-rich B-cell lymphoma and lymphocyte-predominant Hodgkin's disease: two closely related entities? 855 94

Mediastinal large B cell lymphomas are uncommon neoplasms that are thought to originate from thymic B cells. An unusual feature of these neoplasms is that they often lack surface immunoglobulin (Ig), a molecule ubiquitously expressed by most mature B cells. In the present study we have analyzed 12 cases of mediastinal large B cell lymphoma for the expression of the mb-1/CD79a polypeptide. This is a component, together with B29/CD79b, of a heterodimer that is associated with surface Ig on normal B cells. Our aim was to see whether loss of Ig in this type of lymphoma is associated with loss of the accompanying CD79a molecule. We have also evaluated 128 B cell lymphomas of other categories to see whether any of them show discordance between mb-1 and Ig expression and analyzed 30 T cell lymphomas as Ig-negative controls. We found that 5 of the 7 mediastinal large B cell lymphomas with interpretable staining results for both mb-1 and Ig, lack Ig but expressed CD79a (mb-1). This phenotype was very rare in other categories of B cell lymphoma, being found among 110 cases in only 5 cases that were all follicular lymphoma. The remaining 105 B cell lymphomas displayed mb-1+/Ig+ phenotype. All 30 T cell lymphomas were mb-1 negative. We conclude that discordant mb-1/Ig expression occurs commonly in mediastinal large B cell lymphomas. In addition, the finding that 11 of 12 of these neoplasms express a phenotype (CD10-, CD19+, CD20+, CD21-, CD22+, CD23-/+) that is very similar to that described for thymic medullary B cells reinforces the idea that most mediastinal large B cell lymphomas are of thymic B cell origin. The correlation between mb-1 and Ig staining patterns in B cell lymphomas of other categories reveals that in the majority (90%), expression of the antigen receptor complex parallels that of mature B cells. These data therefore confirm that the expression of the mb-1 protein provides independent strong evidence for the B lineage of lymphomas and may be used for their routine phenotypic characterization.
 ...
PMID:Discordant expression of immunoglobulin and its associated molecule mb-1/CD79a is frequently found in mediastinal large B cell lymphomas. 788 54

We have recently shown that an evolutionary conserved gene LAZ3, encoding a zinc finger protein, is disrupted and overexpressed in some B-cell lymphomas (mainly with a large cell component) that show chromosomal rearrangements involving 3q27. Because the breakpoints involved in these rearrangements are focused in a narrow major translocation cluster (MTC) on chromosome 3, we used genomic probes from this region to study the molecular rearrangements of LAZ3 in a large series of patients (217) with non-Hodgkin's lymphoma (NHL). Southern blot analysis showed LAZ3 rearrangement in 43 patients (19.8%). Rearrangement was found in 11 of the 84 patients (13%) with follicular lymphoma but was most frequent in aggressive lymphoma (diffuse mixed, diffuse large cell, and large cell immunoblastic subtypes), in which 31 of the 114 patients (27%) were affected. The highest proportion of LAZ3 alteration was observed in B-cell aggressive lymphoma (26 of 71 cases, 37%). Eleven of the 32 patients with 3q27 chromosomal abnormality had no LAZ3 rearrangement, suggesting the possibility of LAZ3 involvement outside the MTC. On the other hand, 18 of the 39 patients with LAZ3 rearrangement and available cytogenetic results did not have visible chromosomal break at 3q27, suggesting that almost a half of the rearrangements are not detectable by cytogenetic methods. No statistical association could be found between LAZ3 status and initial features of the disease or clinical outcome in either follicular or aggressive lymphomas. We conclude that LAZ3 alteration is a relatively frequent event in B-cell lymphoma, especially in those of aggressive histology. It could be used as a genomic marker of the disease, and further studies are needed to clarify clinical implications of these alterations.
 ...
PMID:LAZ3 rearrangements in non-Hodgkin's lymphoma: correlation with histology, immunophenotype, karyotype, and clinical outcome in 217 patients. 816 31

The principal objective of this study was to investigate whether follicular center cell lymphomas occur among B-cell lymphoma of mucosa-associated lymphoid tissue (MALT). We used a molecular genetic/immunohistochemical approach and analysed 21 cases with the primary site in the gastrointestinal tract. Only two bcl-2 gene rearrangements were detected in our series and were found in two out of seven lymphomas with a nodular growth pattern. A chromosomal translocation t(14;18) was demonstrated by comigration of rearranged bcl-2 and JH sequences in one of these two cases. Additionally, both lymphomas showed bcl-2 protein positive neoplastic follicles, CD10 expression, and lack of vimentin. Therefore, these two cases were defined as follicular lymphomas. In contrast to the two follicular lymphomas of MALT, three other, nodular growing, bcl-2 protein positive lymphomas were found to have no bcl-2 gene rearrangements, to be CD10 negative and to express vimentin. These three lymphomas might be composed of neoplastic extrafollicular cells which secondarily invaded reactive follicles. We conclude that the presence of bcl-2 protein positive follicles is consistent with both a follicular and extrafollicular origin of a B lymphoma of MALT. However, the detection of a bcl-2 gene rearrangement is the most valuable criterion in such a situation, and additional immunophenotypic criteria, such as CD10 expression and lack of vimentin within the neoplastic population, further substantiate the diagnosis of a follicular lymphoma in MALT.
 ...
PMID:Bcl-2 gene rearrangements in primary B-cell lymphoma of the gastrointestinal tract reveal follicular lymphoma as a subtype. 842 81

Mutations of p53 have been suggested to be involved in the histologic transformation of follicular lymphoma, but the role of the retinoblastoma (RB) gene, another tumor suppressor gene, in lymphomagenesis has not been established. To determine the roles of these tumor suppressor genes and their relationship with the anti-apoptotic bcl-2 gene in follicle center lymphoma, the immunohistochemical expression of p53, bcl-2, and RB proteins was correlated with cytologic grade in 50 cases of follicular lymphoma, and the results were compared to 23 cases of diffuse large B-cell lymphoma. The results showed that only 2 of 25 grade 1 follicular lymphoma were p53-positive compared to 16 of 25 grade 3 cases (P <.0001). A significantly lower number (13 of 25) of grade 3 follicular lymphomas expressed bcl-2 compared to grade 1 cases (23 of 25) (P <.004). Eight of 14 bcl-2-negative follicular lymphomas expressed p53, compared with 10 of 36 bcl-2-positive cases (P = .1). Twenty-four of 25 grade 3 follicular lymphomas showed 2+ to 3+ staining for RB protein compared to 9 of 21 grade 1 cases (P <.0002). Expression of p53 protein correlates significantly with higher cytologic grade in follicular lymphoma. Similar to earlier studies of breast cancer and lymphoma, there appears to be an inverse relationship between p53 and bcl-2 expression in follicular lymphoma. Inactivation of the retinoblastoma gene does not seem to be involved in the histogenesis of follicle center lymphoma or diffuse large B-cell lymphoma.
 ...
PMID:Immunohistochemical detection of p53, bcl-2, and retinoblastoma proteins in follicular lymphoma. 862 59

The product of the retinoblastoma tumor-suppressor gene (pRB), a nuclear phosphoprotein that regulates transcription factors such as E2F, is involved in cell cycle control and differentiation. Its activity is regulated by phosphorylation; the underphosphorylated form inhibits transcription whereas the highly phosphorylated form is inactive. Cyclin D1 and its associated kinase (CDK 4/6) phosphorylate pRB in vitro, and therefore are thought to contribute to the regulation of pRB function. To examine the effect of cyclin D1 overexpression on pRB in primary tumor tissue, we studied pRB expression in low-grade B-cell neoplasms, with particular regard to mantle cell lymphoma, which is characterized by cyclin D1 (bcl-1) overexpression. pRB expression was studied by immunostaining with a well-characterized anti-pRB antibody; the phosphorylation status of pRB was examined by immunoblots; and the functional binding capacity of pRB was examined by in vitro binding to adenovirus E1A protein. We studied 3 reactive lymph nodes, 28 low grade B-cell lymphomas, 4 cases of hairy cell leukemia (HCL) and 3 plasmacytomas. Reactive lymph nodes showed intense pRB staining of germinal centers, with strongest (2+) staining in the large cells (centroblasts) of the proliferating (dark) zone and weak or no staining of small lymphocytes, including those of the mantle zone. In B-chronic lymphocytic leukemia (B-CLL) (4 cases), follicular lymphoma (3 cases) and mucosa-associated (MALT) lymphoma (3 cases) strong (2+) pRB staining was limited to centroblasts in reactive and neoplastic follicles and occasional proliferation centers, with only faint staining of small lymphoid cells. In contrast, 15 of 16 cases of mantle cell lymphoma showed strong (1-2+) staining of most cells; one blastoid mantle cell lymphoma showed only faint pRB staining. All cases of (HCL) and plasmacytoma showed strong pRB staining. Although most lymphomas with strong pRB expression were cyclin D1(+), three cyclin D1(+) cases showed only weak pRB expression (1 B-CLL, 1 blastoid mantle cell, 1 unclassifiable low grade B-cell lymphoma). Conversely, of the 4 pRB(+) HCLs and 3 pRB(+) plasmacytomas, only 1 of each was cyclin D1(+). pRB appeared to exist primarily in the underphosphorylated (fastest migrating) form on Western blot, despite the fact that cyclin D1 was complexed to CDK4, a form in which it normally phosphorylates pRB. In addition, pRB appeared to be unmutated, because it bound normally to the adenovirus E1A protein and showed nuclear localization by immunostaining. We conclude that most cases of mantle cell lymphoma, HCL, and plasmacytoma show high levels of pRB in contrast to follicle center lymphoma and small lymphocytic lymphoma; however, pRB expression does not appear to be consistently related to cyclin D1 overexpression. The pRB appears to be unmutated and underphosphorylated, and therefore should be in its active form. Our data from primary lymphoma tissue suggests that overexpression of cyclin D1, whereas tumorigenic, does not lead to pRB loss or hyperphosporylation. Thus, the mechanism by which cyclin D1 contributes to tumorigenesis and the significance of the restricted expression of pRB in low-grade lymphoid neoplasms remain to be determined.
 ...
PMID:Expression of the retinoblastoma protein in low-grade B-cell lymphoma: relationship to cyclin D1. 870 83

The differences between reactive and malignant processes are sometimes blurred. Homogeneity is no longer a requisite for the diagnosis of lymphoma, as witnessed in mucosa-associated lymphatic tissue lymphoma and T-cell-rich B cell lymphoma, which are composed of an admixture of neoplastic clonal B cells and reactive T cells which occasionally are very prominent in the histological picture. Infectious mononucleosis, anaplastic large cell lymphoma, composite lymphoma and Hodgkin's disease, all share many similarities and may actually represent a continuous spectrum of pathological conditions. Immunodeficiency states, whether primary or acquired, are commonly associated with clonal lymphatic malignancies preceded by a polyclonal lymphoproliferative stage, which is usually reversible by reducing immunosuppression. The distinction between these stages is sometimes difficult to assess. Immunologists have so far failed to find a lymphatic tumor-specific antigen, hence, monoclonality is usually based on a constellation of factors, namely homogeneity of the phenotypic expression of few antigens, aberrant expression of antigens and restricted expression of kappa- or lambda-chains in malignancies expressing surface immunoglobulins. Nonrandom chromosomal translocations as well as other aberrations, usually important in the diagnosis of malignancy, are sometimes of limited value. This is mainly due to the existence of translocations [like t(14;18) and t(2;5)] in nonmalignant states, and their non-specificity [the existence of t(8;14) in Burkitt's lymphoma and large cell lymphoma, t(2;5) in Hodgkin's disease and anaplastic large cell lymphoma, and t(14;18) in large cell lymphoma evolving from follicular lymphoma and Burkitt's lymphoma]. The diagnostic tools available in 1995, although usually sufficient, are sometimes unable to distinguish between malignancy and reactivity. Some problematic cases will be more accurately defined as lying in the gray zone, or as belonging to a spectrum ranging between reactivity and malignancy.
 ...
PMID:The gray zone between malignant and reactive processes in lymphoproliferative diseases. 887 7

We report on two cases of low grade follicle centre cell lymphoma with a pronounced parafollicular monocytoid/ marginal zone B-cell component. One patient had a history of preceeding follicular high grade B-cell lymphoma of centroblastic type showing the same light chain restriction and identical immunoglobulin heavy chain gene rearrangement as the low grade lymphoma diagnosed 15 months later. Morphologically, in both cases the two constituents of the low grade tumours were clearly distinguishable. Immunohistochemically, the follicular component strongly expressed bcl-2 protein in contrast to a weak staining of the marginal zone B-cell component. Performing PCR, a rearrangement of the major breakpoint region of bcl-2 was not found. Identical light chain restriction of the follicular and the monocytoid B-cell/marginal zone components strongly indicates a clonal relationship between them. A monocytoid/marginal zone B-cell component in follicular lymphoma probably results from differentiation of the follicle centre cells and does not indicate a composite lymphoma.
 ...
PMID:Monocytoid/marginal zone B-cell differentiation in follicle centre cell lymphoma. 888 47


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>