Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoid cancer. The classical chemotherapy regimen given to these patients was the CHOP (Cyclophosphamide, Hydroxydaunorubicin or Adriamycin, Oncovin or Vincristine, Prednisone or Prednisolone), but recently rituximab with CHOP (R-CHOP) increased the number of cases responding to first line therapy. DLBCL classification identified three principle subgroups. The first one, named germinal centre B cell-like (GCB), responds to both CHOP and R-CHOP treatment and it is mainly characterised by the expression of markers like Bcl-6 and CD10. The second, the activated B-cell like (ABC), has a worse prognosis in comparison with GCB, and is mainly characterised by the expression of IRF-4, PRDM1 and NF-kappaB. It is interesting to notice that IRF-4 and PRDM1 are under the transcriptional control of NF-kappaB, whose high activation level is associated with a worse prognosis. The third one, mediastinal large B-cell lymphoma (PMBCL) is an uncommon subtype characteristically found in young females. Gene expression profiling suggests that this disease resembles Hodgkin lymphoma more than other types of DLBCL. The impact of rituximab on the outcome of patients with PMBCL has still not been fully assessed. It was seen that rituximab inhibits NF-kappaB pathway in vitro. However, the clinical significance of this finding is still unknown, because both ABC and GCB DLBCL show a significant improvement of overall survival after R-CHOP treatment. In this review, the NF-kappaB pathway is suggested as a target for new chemotherapy strategies based on the association of CHOP with molecules more effective than rituximab in this pathway inhibition.
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PMID:Recent prognostic factors in diffuse large B-cell lymphoma indicate NF-kappaB pathway as a target for new therapeutic strategies. 1902 Oct 48

Burkitt lymphoma is a highly aggressive non-Hodgkin lymphoma with endemic, sporadic, and immunodeficiency-associated clinical variants composed of monomorphic medium-sized B cells with a high proliferation rate and a translocation involving the C-MYC locus. Classically, the immunophenotype of Burkitt lymphoma has been considered to be the germinal center type. In most reports, all cases of Burkitt lymphoma are reported to be multiple myeloma 1-negative. multiple myeloma 1 expression is seen in plasma cells and in a small fraction of B cells located in the light zone of germinal centers corresponding to the final step of intra-germinal center B-cell differentiation, and in activated T cells. Therefore, multiple myeloma 1 expression may denote the final step of intra-germinal center B-cell differentiation at the centrocyte stage, as well as the subsequent steps of B-cell maturation toward plasma cells. Unlike most normal germinal center B cells, in which the expression of multiple myeloma 1 and bcl-6 are mutually exclusive, the tumor cells in approximately 50% of multiple myeloma 1-positive DLBCL show coexpression of bcl-6, suggesting that the expression of these proteins may be deregulated. Twenty-five Burkitt lymphoma cases, including 19 associated with HIV, were reported in one of the few studies in the literature; 2 of these cases showed occasional multiple myeloma 1-positive cells, less than the 20% cutoff for positivity. We studied 222 cases of well-characterized Burkitt lymphoma with the classic phenotype and C-MYC translocation and found 90 cases (40.5%) with multiple myeloma 1 nuclear expression, suggesting a late germinal center stage of differentiation.
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PMID:Frequent expression of multiple myeloma 1/interferon regulatory factor 4 in Burkitt lymphoma. 1914 81

The current model of Epstein-Barr virus (EBV) infection and persistence in vivo proposes that EBV uses the germinal center (the GC model) to establish a quiescent latent infection in otherwise-normal memory B cells. However, the evidence linking EBV-infected cells and the GC is only indirect and limited. Therefore, a key portion of the model, that EBV-infected cells physically reside and participate in GCs, has yet to be verified. Furthermore, recent experiments suggested that upon infection of GC cells the viral growth latency transcription program is dominant and GC functionality and phenotype are ablated, i.e., EBV infection is not consistent with GC function. In this study we show that in vivo, EBV-infected B cells in the tonsils retain expression of functional and phenotypic markers of GC cells, including bcl-6 and AID. Furthermore, these cells are physically located in the GC and express a restricted form of latency, the default latency program. Thus, the EBV default latency transcription program, unlike the growth latency program, is consistent with the retention of GC functionality in vivo. This work verifies key components of the GC model of EBV persistence and suggests that EBV and the GC can interact to produce the latently infected memory cells found in the periphery. Furthermore, it identifies latently infected GC B cells as a potential pathogenic nexus for the development of the EBV-positive, GC-associated lymphomas Hodgkin's disease and Burkitt's lymphoma.
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PMID:The intersection of Epstein-Barr virus with the germinal center. 1919 89

This review aims to interrelate the major lymphoma types in the current World Health Organization (WHO) classification to construct a framework for understanding and diagnostic application. Multiple morphological, phenotypical and molecular genotypical data are assessed in order to categorise lymphomas into germinal centre (GC) and extracentric (EC) subgroups. GC entities [lymphocyte-predominant Hodgkin, follicular, Burkitt's, angioimmunoblastic T-cell and diffuse large B-cell lymphoma (DLBCL) with GC profile] express bcl-6, CD10 and/or the GC-homing chemokine CXCL13, and harbour ongoing somatic hypermutations (SHM), but not Epstein-Barr virus (EBV) in its higher latency states. Post-GC entities [classical Hodgkin, marginal zone and lymphoplasmacytic lymphomas, half of chronic lymphocytic leukaemia (CLL)/small lymphocytic lymphoma (SLL), DLBCL with 'activated' or post-GC profile, primary effusion lymphoma, plasmacytoma and myeloma] express, instead, MUM.1 and/or CD138, harbour static rather than ongoing SHM, and may harbour EBV in higher latency states. The remainder of CLL/SLL and the majority of mantle cell lymphoma without SHM constitute the pre-GC ('naive') category, with coexpression of IgD and CD5. Lymphomas can be categorised across lineage (B- or T-cell) and relationship against host immune response (Hodgkin or non-Hodgkin) into GC and EC groups, affording leverage in their differential diagnosis.
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PMID:A practical approach to the understanding and diagnosis of lymphoma: an assessment of the WHO classification based on immunoarchitecture and immuno-ontogenic principles. 1940 43

Diffuse large B-cell lymphoma (DLBCL) forms a heterogeneous collection of aggressive non-Hodgkin's Lymphoma in which three principle classes of neoplasia have been defined according to gene expression and immunophenotyping studies. The present investigation sought to examine the immunophenotype of proposed subgroups and relate these to patient survival. A series of 155 DLBCL treated uniformly with anthracycline therapy in clinical trials, were stratified upon the basis of common biomarker expression with combination immunophenotype being related to patient overall survival. Stratification of tumours with respect to combined expression profiles of the three biological markers (CD10, Bcl-6 and MUM-1) revealed six groups showing significant differences in survival (p=0.014). The greatest difference resided between distinct populations of germinal centre (GC) cell tumours; the first being CD10-, Bcl-6+, MUM-1- and the second CD10+ Bcl-6+ MUM-1+ (p=0.002). The former group displayed median survival time of 143 months, the latter only 11 months. A third population of GC tumours (CD10+ Bcl-6+ and MUM-1-) also displayed a relative short median survival (32 months). Of the three groups presenting a non-GC or activated B cell (NGC/ABC) phenotype, only one (CD10-, Bcl-6+ and MUM-1+) presented short-term median survival (27 months) comparable with poor prognosis GC sub-populations. Within the remaining ABC tumour groups (CD10- Bcl-6- MUM-1- and CD10- Bcl-6- MUM-1+) patients presented intermediate median survival times of 54 and 58 months, respectively. Thus, the GC phenotype did not act as a universal indicator of good clinical prognosis, but rather multiple groups of GC tumours were associated with distinct overall survival profiles. Ultimately, the data allowed definition of a predictive algorithm defining three groups predicting poor, intermediate and good clinical prognosis. The first of these comprised two patient sub-populations with GC-like tumours together with one sub-population of NGC/ABC, the second two sub-populations of ABC-like tumours, and the final a single group of GC-like tumours associated with optimal long-term survival.
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PMID:Immunophenotyping of diffuse large B-cell lymphoma (DLBCL) defines multiple sub-groups of germinal centre-like tumours displaying different survival characteristics. 1978 48

The paper describes a rare case of invasive lobular carcinoma with the diffuse growth type simulating malignant non-Hodgkin lymphoma. The immunohistochemical study of the tumor established a marked expression of pancytokeratin, GSDFP-15, receptors to estrogen and progesterone, CD 7, Bcl-2, expression CD 3, CD 5, CD 10, CD 20, CD 23, CD 30, ALK, Bcl-6, inactive expression of E-cadherin. The ability of invasive lobular carcinoma to simulate malignant non-Hodgkin lymphoma determines the diagnostic value and significance of an immunohistochemical study to confirm the epithelial nature of the tumor.
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PMID:[A rare case of small-cell diffuse invasive breast lobular carcinoma]. 1982 33

Class III beta-tubulin (TUBB3) expression in carcinoma is associated with resistance to tubulin-binding chemotherapeutic agents. Recently, follicular dendritic cells (FDCs) were reported to express TUBB3 under physiologic conditions. We investigated TUBB3 expression in a wide range of lymphoproliferative disorders using immunohistochemistry. Dual immunostaining for Bcl-6 and TUBB3 revealed that some germinal center B cells also express TUBB3 in addition to FDCs. In Hodgkin lymphomas (HLs), 47.1% (40/85) expressed TUBB3 in the tumor cells with an all-or-none pattern. TUBB3 expression in HL was more common in mixed cellularity type than nodular sclerosis type (P=0.032). Among non-HLs, 79.3% (23/29) of anaplastic large cell lymphoma (ALCL), 8% (2/25) of extranodal natural killer/T-cell lymphoma, and 75% (21/28) of Burkitt lymphoma showed TUBB3 expression with an all-or-none pattern. Of diffuse large B-cell lymphoma, 15.2% (32/210) expressed TUBB3 in a heterogeneous pattern. In ALCL, TUBB3 expression was more common in systemic ALCL than in primary cutaneous ALCL (P=0.046). Diffuse large B-cell lymphomas with a germinal center B-like subgroup exhibited TUBB3 expression more frequently than non-GCB-like subgroup (P=0.01). Otherwise, none of the 18 angioimmunoblastic T-cell lymphomas; 18 peripheral T-cell lymphomas, not otherwise specified; 12 follicular lymphomas; 62 marginal zone lymphomas; 7 mantle cell lymphomas; 8 small lymphocytic lymphomas; or 2 FDC sarcomas expressed TUBB3. In angioimmunoblastic T-cell lymphoma and Castleman disease, TUBB3 was positive in immunoblasts corresponding to Epstein-Barr virus-infected or Kaposi sarcoma herpes virus-infected cells. A variety of neoplastic and non-neoplastic lymphoproliferative disorders exhibited characteristic TUBB3 expression patterns; these results suggest potential for diagnostic utility, some insight into the pathobiology of TUBB3 expression, and potential therapeutic implications.
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PMID:Class III beta-tubulin shows unique expression patterns in a variety of neoplastic and non-neoplastic lymphoproliferative disorders. 2022 May 12

Among B-cell non-Hodgkin's lymphomas, neural cell adhesion molecule/CD56 expression is exceptional. In this study, seven cases of CD56-positive diffuse large B-cell lymphoma (DLBCL) are described. The frequency of CD56-positive DLBCL was 7% in our hospital. Four of seven (57.1%) cases expressed both CD10 and bcl-6 suggestive of a germinal center B-cell phenotype. Six of seven (85.7%) cases expressed bcl-6. Two cases expressed aberrant T cell-associated antigens, one each of CD7 and CD8. However, none of these seven cases showed CD5 expression. No significant difference was observed between CD56-positive and CD56-negative DLBCL in terms of the five international prognostic index risk factors. However, all seven cases had at least one extranodal involvement and showed a good response to initial treatment. The predominance of extranodal involvement in our series may be associated with the adhesion-related function of CD56. A high frequency of bcl-6 expression may be associated with a more favorable clinical course and prognosis.
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PMID:CD56-positive diffuse large B-cell lymphoma: possible association with extranodal involvement and bcl-6 expression. 2055 74

B-cell activating factor receptor (BAFF-R) is one of three known receptors for BAFF. BAFF-R is required for B-cell maturation and survival. We tried to determine the normal pattern of BAFF-R expression in non-neoplastic and neoplastic B- and T-cells. We used immunohistochemistry to evaluate the expression pattern of BAFF-R in non-neoplastic and neoplastic lymphoid tissues of routinely fixed paraffin-embedded samples, and examined the relationships among BAFF-R and expressions of CD10, bcl-6, MUM-1, and MIB-1. BAFF-R expression was detected on B-cells of the mantle zones, some cells within germinal centers, and scattered cells in the interfollicular areas of reactive lymph nodes. BAFF-R expression was only found in B-cell lymphoma (60/120, positive samples/examined samples), but not in T/NK cell lymphoma (0/10) or Hodgkin lymphoma (0/10). The proportions were as follows : follicular lymphoma (14/16), diffuse large B-cell lymphoma (DLBCL) (27/61), mantle cell lymphoma (4/4), and Burkitt lymphoma (0/4). According to Hans' criteria, DLBCLs were subclassified into germinal center B-cell-like (GCB) and non-germinal center B-cell-like (non-GCB) types. Interestingly, in nodal lymphomas, in the GCB subgroup (n=12), 9 of 12 (75%) were positive for BAFF-R, while 6 of 20 (30%) were positive in the non-GCB subgroup (n=20) (p < 0.05). In addition, expression of BAFF-R related to lower MIB-1 index was associated with GCB-type DLBCL. In conclusion, BAFF-R was only found in some B-cell lymphomas, which was closely associated with the expression pattern in normal counterparts, although BAFF-R expression on follicular lymphoma is different from that on germinal center cells, which is similar to bcl-2. BAFF-R was rather specifically related to low growth activity of GCB-type DLBCL of nodal origin.
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PMID:BAFF-R is expressed on B-cell lymphomas depending on their origin, and is related to proliferation index of nodal diffuse large B-cell lymphomas. 2112 70

This study was aimed to investigate the clinical characteristics and treatment of patients with autoimmune disease combined with non-Hodgkin lymphoma (NHL). The clinical characteristics and pathologic patterns of 6 patients with NHL who concurrently suffered from autoimmune diseases were analysed retrospectively from aspects of clinical course, pathologic features, and therapy. Treatment outcomes for autoimmune diseases and NHL were observed. The results showed that 6 patients included 4 females and 2 males, range in age from 28 to 65 years with a median age of 56 years. The autoimmune diseases are Sjogren's syndrome (SS, 2 cases), rheumatoid arthritis (RA, 2 cases), ulcerative colitis (UC, 1 case) and Crohn's disease (CD, 1 case). The NHL diseases located not only in the lymph node (n = 3) but also in extranodal sites (n = 3). Histologically, 3 cases were diffuse large B cell lymphoma (DLBCL), 2 cases were extranodal nasal NK/T lymphoma (ENKL) and 1 case was peripheral T cell lymphoma, not otherwise specified. Based on CD10, Bcl-6 and MUM1 expression patterns, all 3 DLBCL were classified as non-GC subtype. EBER positive tumor cells were detected in 2 case of ENKL. 5 patients achieved a complete remission (83%) and 1 patient was primary drug-resistant after CHOP chemotherapy or involved radiotherapy. Median survival from the time of lymphoma diagnosis was 3 years. 1 patient showed clinical improvement of the SS symptoms, 2 patients (CD and UC) showed stable state of disease and 2 patients with RA and 1 patient with SS needed continuing treatment for their autoimmune diseases after chemotherapy for NHL. It is concluded that the development of NHL is one of the most serious complications in patients with autoimmune diseases. There is an increased frequency of non-GC subtype DLBCL. CHOP combined with or without radiotherapy proves to be effective for autoimmune disease patients with aggressive NHL but ineffective for concurrent autoimmune diseases.
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PMID:[Clinic-pathologic characteristics of autoimmune diseases combined with non-Hodgkin's lymphoma]. 2136 36


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