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)

We report a 68-year-old Korean man presenting with asymptomatic erythematous polycyclic annular firm plaques on his back that spread to the right shoulder. Histopathologic examination showed dense, diffuse infiltrates involving the entire dermis, consisting of atypical lymphocytes with many centrocytes and a few centroblasts. Spindle-shaped cells with elongated, twisted nuclei containing dispersed chromatin were also seen. Immunohistochemical analysis showed that all of the cells were strongly positive for CD20, CD21, CD79a and CD45, while they were negative for CD3, CD5, CD10, CD23, CD35, CD43, CD45RO and CD68. The spindle cells were also negative for smooth-muscle actin, desmin, S-100 and CD34. They consistently expressed nuclear bcl-6, but did not express bcl-2, multiple myeloma-1 and p16. We diagnosed him with primary cutaneous spindle cell B-cell lymphoma (PCSBCL) and treated him with six cycles of cyclophosphamide, adriamycin, vincristine, prednisone and rituximab (R-CHOP) chemotherapy; his skin lesions disappeared completely. Immunohistochemical profiles suggest that PCSBCL is a variant of primary cutaneous follicle center lymphoma.
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PMID:Primary cutaneous spindle cell B-cell lymphoma with multiple figurate erythema-like manifestation. 1912 34

The classification of germinal centre (GC) and non-GC is an important prognostic immunophenotype for patients with diffuse large B cell lymphoma (DLBCL) following anthracycline-based chemotherapy. The expression of the anti-apoptotic protein, Bcl-2, has been associated with an unfavourable prognosis in patients with DLBCL. Immunohistochemistry was performed using antibodies against CD10, Bcl-6, MUM-1 and Bcl-2. To establish the combined prognosis of the immunophenotype and Bcl-2 overexpression, patients were separated into four subgroups based on their gene expression profile: the Bcl-2 positive GC subgroup, Bcl-2 negative GC subgroup, Bcl-2 positive non-GC subgroup, and the Bcl-2 negative non-GC subgroup. The clinical characteristics and survival outcomes of the four patient subgroups were compared. Ninety-six patients with de novo DLBCL received R-CHOP (rituximab, cyclophosphamide, vincristine, adriamycin and prednisone) therapy. The baseline characteristics of the patient subgroups were similar. The Bcl-2 negative GC subgroup had a favourable progression-free and overall survival (OS) compared with the other three subgroups (p = 0.042, 0.043). Multivariate analysis confirmed that the Bcl-2 negative GC group was independently associated with progression-free survival and OS. The results of this study showed that the Bcl-2 negative GC patients had the most favourable prognosis among patients with DLBCL that received R-CHOP.
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PMID:Prognostic significance of the Bcl-2 negative germinal centre in patients with diffuse large B cell lymphoma treated with R-CHOP. 1915 70

This study was purposed to explore the expressions of bcl-6, lpp and miR-28 genes in diffuse large B cell lymphoma (DLBCL) cell lines at the levels of gene and protein, and the relationship between them. Northern blot was used to detect bcl-6 and lpp mRNA expression in 8 DLBCL cell lines. Solution hybridization was used to measure miR-28 expression, and Western blot was performed for BCL-6 and LPP protein determinations. The results showed that the expression of bcl-6 mRNA was higher in the cell lines with Ig/BCL-6 translocation (Oc1-ly8, MD903, CTB-1, and MD901), and negative in those without Ig/BCL-6 translocation (HRC57 and K231). The expression of lpp mRNA in CTB-1 cell line was negative. MiR-28 was positive in all cell lines, and the expression levels from high to low were in line as follows: K231, CTB-1, MD903, HRC57, MD901, RCK8, OC1-LY8 and BEVA. BCL-6 protein was also positive in all of cell lines, and the expression levels from high to low were as follows: RCK8, BEVA, MD901, CTB-1, MD903, OC1-LY8, HRC57 and K231. LPP protein was negative in K231 cells, and the expression levels in other cells from high to low were line up as follows: HRC57, OC1-LY8, BEVA, RCK8, CTB-1, MD901 and MD903. The expression levels of bcl-6 and lpp mRNA were not consistent with expression levels of protein. It is concluded that the gene expression levels of bcl-6, lpp and miR-28 are different in various DLBCL cell lines. The expression levels of bcl-6 and lpp mRNA are not parallel with expression levels of protein. The roles of bcl-6, lpp and miR-28 in initiation and development of DLBCL need further investigation.
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PMID:[Expressions of bcl-6, lpp and miR-28 genes in diffuse large B cell lymphoma cell lines]. 1923 53

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

Gene expression profiling studies initially enabled diffuse large B-cell lymphoma to be divided into germinal center and activated B-cell-like subtypes, which define high- and low-risk patient groups when treated with chemotherapy. Attempts to reproduce the prognostic classification immunohistochemically have, however, provided inconsistent results. The aim of this study was to determine whether modified immunohistochemical classification of cell of origin focusing on activated B-cell-like markers could be used to predict the outcome of immunochemotherapy-treated diffuse large B-cell lymphoma patients. The expression of CD10, Bcl-6, MUM1/IRF4, Bcl-2, and FOXP1 was determined immunohistochemically from 88 samples of diffuse large B-cell lymphoma patients treated uniformly with R-CHOP. When the modified classification using MUM1/IRF4 and FOXP1 positivities as activated B-cell-like markers was applied to distinguish the patients between the activated B-cell-like and other diffuse large B-cell lymphoma subtypes, a significantly worse outcome was seen for the patients with the activated B-cell-like phenotype (3-year failure-free survival 63 vs 82%, P=0.048, overall survival 69 vs 85%, P=0.110). Similarly, according to the Muris algorithm, the group 2 patients representing Bcl-2-positive post-germinal center patients showed an inferior outcome in comparison to the group 1 patients (failure-free survival 59 vs 81%, P=0.041, overall survival 67 vs 82%, P=0.159). In contrast, when the classification of the same cohort was performed according to the Hans algorithm, no significant difference in survival was observed between the germinal center and non-germinal center patients. In conclusion, the data suggest that both the modified activated B-cell-like and Muris classifications define the non-germinal center phenotype as an adverse risk factor in R-CHOP-treated diffuse large B-cell lymphoma patients.
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PMID:Prognostic impact of activated B-cell focused classification in diffuse large B-cell lymphoma patients treated with R-CHOP. 1944 93

We present a case of primary cutaneous diffuse large B-cell lymphoma, leg type, with an unusual clinical picture. A 41-year-old man presented with a 2-year history of slowly progressive plaques, nodules, and garland-like patches on his chest, right upper arm, and back. Complete staging investigations revealed no extracutaneous involvement. Histological examination of a nodule revealed a diffuse nonepidermotropic infiltrate mainly composed of large blast cells with features of immunoblasts and centroblasts and spindle cells seen at the periphery of the infiltrate. Histological examination of a garland-like lesion showed perivascular infiltrates composed predominantly of small lymphocytes admixed with only occasional large blasts. The blasts from the nodule and garland-like lesions and spindle cells identified in the nodule exhibited an identical phenotype: they stained positively for CD20, CD79a, and bcl-2 and tested negative for bcl-6, CD5, CD10, and TdT. CD35 revealed no networks of follicular dendritic cells. Widespread garland-like lesions are not a typical feature of primary cutaneous diffuse large B-cell lymphoma.
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PMID:Unusual clinicopathological presentation of primary cutaneous diffuse large B-cell lymphoma, leg type, with multiple nodules and widespread garland-like lesions. 1946 Dec 42

Primary CNS diffuse large B-cell lymphoma (CNS DLBCL) is confined to the CNS, and constitutes a distinct entity. In the present study a series of 40 Japanese patients with CNS DLBCL who presented with neurological, but not systemic symptoms, was reviewed. Median survival was 18.7 months. CD5, CD10, Bcl-6, MUM-1, and Bcl-2 were positive in 30%, 10%, 84%, 100%, and 93% of patients, respectively. All CD10-negative patients had non-germinal center B-cell type. There was no significant difference in survival among the immunophenotypic subgroups. CNS DLBCL appeared to be homogenous as a group, which prompted the comparison with another distinct extranodal entity, intravascular large B-cell lymphoma (IVLBCL) in Japanese patients. CNS DLBCL patients did not differ in age, sex, or immunophenotype, including CD5 positivity, from IVLBCL patients, but were significantly less likely to have poor prognostic parameters than IVLBCL patients: the international prognostic index score was low or low-intermediate in 86% of CNS DLBCL patients and high or high-intermediate in 98% of IVLBCL patients. Notably, despite this difference, their survival curves almost overlapped. The present study highlights the issue of clinical distinctiveness of aggressive extranodal lymphomas, the peculiar migration and localization of which should be further clarified.
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PMID:Comparative clinicopathological study of primary CNS diffuse large B-cell lymphoma and intravascular large B-cell lymphoma. 1956 5

In the germinal center (GC), B cells proliferate dramatically and diversify their immunoglobulin genes, which increases the risk of malignant transformation. The GC B-cell reaction relies on crosstalk with follicular dendritic cells (FDCs), to which the costimulatory receptor CD137 on FDCs and its ligand on GC B cells potentially contribute. We report that mice deficient for CD137 ligand (CD137L) are predisposed to develop B-cell lymphoma, with an incidence of approximately 60% at 12 months of age. Lymphoma membrane markers were characteristic of GC B cells. Longitudinal histologic analysis identified the GC as site of oncogenic transformation and classified 85% of the malignancies found in approximately 200 mice as GC-derived B-cell lymphoma. To delineate the mechanism underlying lymphomagenesis, gene expression profiles of wild-type and CD137L-deficient GC B cells were compared. CD137L deficiency was associated with enhanced expression of a limited gene set that included Bcl-10 and the GC response regulators Bcl-6, Spi-B, Elf-1, Bach2, and activation-induced cytidine deaminase. Among these are proto-oncogenes that mediate GC B-cell lymphoma development in humans. We conclude that CD137L ordinarily regulates the GC B-cell response and thereby acts as a tumor suppressor.
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PMID:Mice deficient for CD137 ligand are predisposed to develop germinal center-derived B-cell lymphoma. 1960 48

We evaluated the usefulness of prognostic markers in patients with diffuse large B-cell lymphoma (DLBCL) treated with cyclophosphamide, vincristine, doxorubicin, and prednisolone (CHOP) +/- rituximab (R-CHOP) in Japan. We studied 730 patients with DLBCL; 451 received CHOP and 279 R-CHOP. We analyzed biopsy samples immunohistochemically for markers of germinal center B cells (CD10, Bcl-6), postgerminal center B cells (Multiple myeloma-1), and apoptosis (Bcl-2). The median follow-up period for surviving patients was 56.4 months for the CHOP group and 25.2 months for the R-CHOP group. DLBCL were categorized as germinal center B (GCB) subtype (352/730; 48.2%) or non-GCB subtype (378/730; 51.8%). In the CHOP group, the high expression of CD10 (P = 0.022) or Bcl-6 (P = 0.021), or GCB subtype (P = 0.05) was associated with better overall survival, whereas the high expression of Bcl-2 (P = 0.001) or MUM1 (P = 0.011), or non-GCB subtype (P = 0.05) was associated with worse overall survival. In the R-CHOP group, however, these biomarkers except Bcl-6 were not significant prognostic factors. The patients with non-GCB subtype showed improved survival in the R-CHOP group (P = 0.756). The International Prognostic Index was a useful clinical marker of survival in the CHOP group (P < 0.001) and also in the R-CHOP group (P < 0.001). Results of improved survival with rituximab addition indicate that the relevance of previously recognized prognostic factors should be re-evaluated.
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PMID:Prognostic impact of immunohistochemical biomarkers in diffuse large B-cell lymphoma in the rituximab era. 1965 56

The aim of this study was to clarify whether diffuse large B-cell lymphoma (DLBCL) with a high number of epithelioid histiocytes (DLBCL-EH) could have distinctive clinicopathological characteristics. Clinicopathological findings in 22 cases with DLBCL-EH and, as a control, 96 cases with ordinary type of DLBCL were analyzed. There were ten men and 12 women with ages ranging from 38 to 91 (median, 64) years. The primary site was lymph node in 16 cases, extranodal organs in three, and unknown in three. Stage of disease was I in five cases, II in three, III in nine, and IV in five. Histologically, there was a diffuse proliferation of large lymphoid cells admixed with numerous clusters of epithelioid histiocytes sprinkling throughout the lesions. Immunohistochemically, the large lymphoid cells were CD20(+), CD15(-), and CD3(-) and positive for CD10, bcl-6, and MUM1 in nine (41%), eight (36%), and 12 (55%) of 22 cases, respectively. Epstein-Barr virus positive rate was higher in DLBCL-EH (23.8%) than that in ordinary DLBCL (4.5%; P<0.05). Clonality analysis revealed monoclonal bands in all of the examined 20 cases with DLBCL-EH. Multivariate analysis revealed the prominent epithelioid reaction to be an independent factor for favorable prognosis. These findings suggest that DLBCL-EH could be a specific morphological variant of DLBCL associated with a better prognosis.
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PMID:Diffuse large B-cell lymphoma with a high number of epithelioid histiocytes (lymphoepithelioid B-cell lymphoma): a study of Osaka Lymphoma Study Group. 1972 7


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