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)

Hedgehog (HH) signaling is important in the pathogenesis of several malignancies. Recently, we described that HH signaling proteins are commonly expressed in diffuse large B-cell lymphoma (DLBCL); however, the functional role of HH pathway in DLBCL has not been explored. Here, we assessed the possibility that HH pathway activation contributes to the survival of DLBCL. We found that HH signaling inhibition induces predominantly cell-cycle arrest in DLBCL cells of germinal center (GC) B-cell type, and apoptosis in DLBCL cells of activated B-cell (ABC) type. Apoptosis after HH signaling inhibition in DLBCL cells of ABC type was associated with downregulation of BCL2; however HH inhibition was not associated with BCL2 downregulation in DLBCL of GC type. Functional inhibition of BCL2 significantly increased apoptosis induced by HH inhibition in DLBCL cells of both types. We also showed that DLBCL cells synthesize, secrete and respond to endogenous HH ligands, providing support for the existence of an autocrine HH signaling loop. Our findings provide novel evidence that dysregulation of HH pathway is involved in the biology of DLBCL and have significant therapeutic implications as they identify HH signaling as a potential therapeutic target in DLBCL, in particular for those lymphomas expressing the HH receptor smoothened.
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PMID:Hedgehog signaling pathway is activated in diffuse large B-cell lymphoma and contributes to tumor cell survival and proliferation. 2020 May 56

Among methotrexate (MTX)-related lymphoproliferative disorders (MTX-LPD), diffuse large B-cell lymphoma (DLBCL) accounts for about half. We studied the clinicopathological characteristics and prognosis of patients with DLBCL in MTX-LPD. This study included 29 patients who developed DLBCL after receiving MTX for rheumatoid arthritis. MTX was discontinued in all patients. Their median age was 62 years. Elevated lactate dehydrogenase (LDH) level was observed in 97% of the patients, bone marrow involvement in 17%, and involvement of extranodal sites in 41%. As for the cellular immunophenotype, CD20 was positive in 93%, CD5 in 3%, CD10 in 31%, BCL2 in 21%, BCL6 in 69%, and Epstein-Barr virus (EBV)-encoded small non-polyadenylated RNA (EBER) in 24%. Chemotherapy was started within 2 months after MTX withdrawal in 23 patients, of whom 12 patients received combination with rituximab. Spontaneous remission occurred in the remaining six patients. The EEBV-positive rate was 67% (4/6), and the four EBV-positive patients achieved complete response. Among the 23 DLBCL patients treated with chemotherapy, 20 patients achieved complete response. The 5-year overall survival was 74% and the 5-year progression-free survival was 65%. After the development of DLBCL, withdrawal of MTX was the first choice of treatment. Germinal center B-cell type and EBER-positive patients tended to show spontaneous remission. The utility of rituximab should be examined in future studies.
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PMID:Clinicopathologic correlations of diffuse large B-cell lymphoma in rheumatoid arthritis patients treated with methotrexate. 2021 Jul 95

The biologic relationship between small B-cell lymphoma and histiocytic sarcoma (HS) when occurring in the same patient remains unclear, though recent data suggest a possible 'transdifferentiation' from follicular lymphoma (FL) to HS. We investigated the clonal relationship in two cases of small B-cell lymphoma with subsequent HS. Case 1: A 62-year-old female with splenic marginal zone lymphoma (SMZL) developed HS in a groin lymph node 1 year after the primary diagnosis. PCR/sequence analysis of the IGH gene showed a monoclonal rearrangement carrying an identical nucleotide sequence of PCR products from the spleen with SMZL and the lymph node with HS. Case 2: A 61-year-old female with a remote history of FL developed supraclavicular lymphadenopathy, which was confirmed to be HS. PCR analysis of the HS detected a monoclonal rearrangement of the IGH gene and FISH analysis revealed IGH/BCL2 fusion, a genetic hallmark for FL. The transformed HSs showed partial retention of their prior B-cell lymphomas' signatures, including expression of OCT2 in both cases and expression of BCL6 and enhanced expression of BCL2 in case 2. Both HSs demonstrated hypermutated IGH variable regions, arguing against a common progenitor mechanism of the transformation process. The data suggest a common clonal origin of B-cell lymphoma and subsequent HS occurring in the same patient, indicating that 'transdifferentiation' occurs in other small B-cell lymphomas, in addition to the previously reported FL or B-cell lymphoma with IGH/BCL2.
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PMID:Histiocytic sarcoma arising in indolent small B-cell lymphoma: report of two cases with molecular/genetic evidence suggestive of a 'transdifferentiation' during the clonal evolution. 2038 55

Published in September 2008, the updated World Health Organization Classification of Tumors of Hematopoietic and Lymphoid Tissues introduces provisional borderline categories for lymphoma cases that demonstrate overlapping clinical, morphological, and/or immunophenotypic features between well-established entities. These overlapping features pose real diagnostic challenges especially in identifying atypical cases of diffuse large B-cell lymphoma, Hodgkin lymphoma, and Burkitt lymphoma. Lymphoma cases showing borderline features between T-cell/histiocyte-rich large B-cell lymphoma and nodular lymphocyte predominant Hodgkin lymphoma are not included within the borderline categories provisionally recognized by the updated classification. Within the borderline categories, there are cases combining features of primary mediastinal large B-cell lymphoma and classical Hodgkin lymphoma. Many of these cases resemble classical Hodgkin lymphoma but have a large number of tumor cells expressing CD20, CD45, and B-cell transcription factors. Alternatively, these cases may resemble primary mediastinal large B-cell lymphoma but contain tumor cells resembling Reed-Sternberg cells and displaying an aberrant phenotype such as CD20(-), CD15(-/+) CD45(+), CD30(+), Pax5(+), OCT2(+/-), and BOB1(+/-). Another new borderline category defining B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma, represents a biologically heterogeneous group. Cases with morphologic features intermediate and with CD10/BCL6 coexpression should be placed in diffuse large B-cell lymphoma/Burkitt lymphoma category if tumor cells also show strong BCL2 staining and/or a Ki67 proliferation index of less than 90%. When MYC rearrangements are present in these cases, the lymphomas often have atypical features, including concurrent rearrangements of BCL2 and/or BCL6 genes (so-called double/triple-hit lymphomas) and more aggressive behavior. For the provisional borderline categories, unresolved issues include understanding molecular pathogenesis and defining an effective treatment.
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PMID:B-cell lymphomas with features intermediate between distinct pathologic entities. From pathogenesis to pathology. 2039 9

Prognostic markers identify subgroups of patients with similar risk profiles, helping to guide clinical care. The addition of rituximab to conventional anthracycline-based chemotherapy has improved clinical outcomes for patients with diffuse large B-cell lymphoma (DLBCL). Studies suggest that rituximab eliminates or modulates the significance of some markers (eg, BCL6 or BCL2), whereas other previously unimportant markers may emerge as significant prognostic indicators in the setting of treatment that now includes rituximab. These changes in the prognostic profile are likely to reflect the impact of rituximab on survival pathways important to some groups of patients with DLBCL but not to other groups, and thereby may provide clues to the underlying biology of the disease. They also identify subgroups of patients likely to benefit most from rituximab therapy and those who seem to garner no advantage from its inclusion in their treatment. Studies of prognostic indicators in the context of modern therapy have the potential to identify new, rational therapeutic targets for this biologically diverse disease.
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PMID:Prognostic markers in diffuse large B-cell lymphoma: Keys to the underlying biology. 2042 75

Mantle cell lymphoma (MCL) is a mature B-cell lymphoma characterized by expression of CD5, overexpression of Cyclin D1 as a result of chromosomal translocation t(11;14)(q13;q32), and poor prognosis. Cases of MCL lacking CD5 expression as well as cases with coexpression of CD5 and CD10 have also been reported. Here we describe an uncommon case of de novo MCL with expression of CD10, but not CD5, mimicking lymphoma of germinal center-derived B cells. The lymphoma cells in this case demonstrated a diffuse pattern of proliferation, and were strongly positive for Cyclin D1 by immunohistochemical stain. Fluorescence in situ hybridization studies demonstrated the presence of t(11;14)(q13;q32) involving BCL1, but not chromosomal translocations involving C-MYC or BCL2, confirming the diagnosis of MCL. This case further highlights the importance of comprehensive immunophenotypic and genetic characterization in the diagnosis and classification of B-cell lymphomas.
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PMID:An uncommon case of de novo CD10+ CD5- mantle cell lymphoma mimics follicle center B cell lymphoma. 2049 Mar 33

Primary lymphomas of the oral cavity are rare and the most frequent type is diffuse large B-cell lymphoma (DLBCL). Recently, several reports have highlighted the value of classifying DLBCL into prognostically important subgroups, namely germinal center B-cell like (GCB) and non-germinal center B-cell like (non-GCB) lymphomas based on gene expression profiles and by immunohistochemical expression of CD10, BCL6 and MUM-1. GCB lymphomas tend to exhibit a better prognosis than non-GCB lymphomas. Studies validating this classification have been done for DLBCL of the breast, CNS, testes and GI tract. Therefore we undertook this study to examine if primary oral DLBCLs reflect this trend. We identified 13 cases (age range 38-91 years) from our archives dating from 2003-09. IHC was performed using antibodies against germinal center markers (CD10, BCL6), activated B-cell markers (MUM1, BCL2) and Ki-67 (proliferation marker). Cases were sub-classified as GCB subgroup if CD10 and/or BCL6 were positive and MUM-1, was negative and as non-GCB subgroup if CD10 was negative and MUM-1 was positive. Immunoreactivity was noted in 2/13 cases for CD10, in 12/13 for BCL6, in 8/13 for MUM-1, and in 6/13 for BCL2. Therefore, 8/13 (58%) were sub-classified as non-GCB DLBCLs and 5/13 (42%) as GCB subgroup. All tumors showed frequent labeling with Ki-67 (range 40-95%). Four of the 8 patients with non-GCB subgroup succumbed to their disease, with the mean survival rate of 16 months. Two patients in this group are alive, one with no evidence of disease and another with disease. No information was available for the other 3 patients in this group. Four of the 5 patients in the GCB subgroup were alive with no evidence of disease and one patient succumbed to complications of therapy and recurrent disease after 18 months. In conclusion, our analysis shows that primary oral DLBCL predominantly belongs to the non-GCB subgroup, which tends to exhibit a poorer prognosis. These findings could allow pathologists to provide a more accurate insight into the potential aggressive behavior and poorer prognosis of these lymphomas.
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PMID:Primary diffuse large B-cell lymphoma of the oral cavity: germinal center classification. 2053 6

BCL2, originally identified as a proto-oncogene in B-cell lymphoma, is a key regulator of apoptosis. Although it is more than 200 kb in length, at least 70% of the t(14;18) translocation in follicular lymphomas occurs at the BCL2 major breakpoint region (mbr), located in the 3'-untranslated region (3'-UTR). We have previously found that the mbr is a regulatory element which positively regulates BCL2 expression and this regulatory function was closely associated with SATB1, which binds to a 37 bp mbr (37 mbr) in the 3'-end of the mbr directly. However, the precise molecular mechanisms by which the mbr regulates gene expression are not fully understood. In this study, we purified Poly(ADP-ribose) polymerase-1 (PARP-1) from the DNA-protein complexes formed by 37 mbr in Jurkat cells and demonstrated that PARP-1 participates in the 37 mbr-protein complex's formation in vitro and in vivo. Functional analysis showed that overexpression of PARP-1 decreases 37 mbr regulatory function and BCL2 expression. Conversely, knockdown of PARP-1 with RNAi increases BCL2 expression. Taken together, the present findings indicate that PARP-1 is a component of BCL2 37 mbr-protein complexes, and PARP-1 is involved in the regulation of BCL2 expression. These findings are helpful in understanding the regulatory mechanisms of BCL2 expression.
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PMID:Poly (ADP-ribose) polymerase-1 binds to BCL2 major breakpoint region and regulates BCL2 expression. 2056 16

Primary cutaneous lymphomas are defined as lymphomas, which are present in the skin without evidence of extracutaneous disease at the time of diagnosis. Primary cutaneous large B-cell lymphoma (PCLBCL) is a subtype of primary cutaneous B-cell lymphoma with a female predominance, occurring in elderly patients and known to have unfavorable prognosis. We evaluated 10 cases of PCLBCL in immunocompetent patients between 2005 and 2008. A panel of immunoperoxidase stains; CD3, CD10, CD20, BCL2, BCL6, and MUM1 were performed on all cases. Nuclear factor kappa B (NF-kappaB) pathway activation was evaluated using an immunostain for P65. The presence of Epstein-Barr virus (EBV) was assessed using Epstein-Barr virus encoded RNA (EBER) in situ hybridization probe. All cases were CD20 positive and CD3 negative. CD10, BCL6, BCL2, and MUM1 were positive in 4/10 (40%), 6/10 (60%), 7/10 (70%), and 7/10 (70%) cases, respectively. NF-kappaB activation was detected in 7/10 (70%) cases. One (10%) case was positive for EBV by in situ hybridization. Interestingly, the EBV positive case was also positive for MUM1 and negative for CD10, indicating an activated immunophenotype. In conclusion, majority of PCLBCL shows activation of NF-kappaB pathway with a low incidence of EBV.
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PMID:Primary cutaneous large B-cell lymphoma shows activation of nuclear factor kappa B and low incidence of Epstein-Barr virus. 2057 44

Lymphomas with 2 translocations involving c-MYC and BCL2 or BCL6 are a subset of biologically aggressive mature B-cell lymphomas now frequently categorized under the entity of B-cell lymphoma, unclassifiable, with features intermediate between Burkitt lymphoma and diffuse large B-cell lymphoma. We identified a cohort of these lymphomas in our databases and retrospectively reviewed corresponding in-house flow cytometric data to determine whether a common immunophenotype might be present. Herein we report on our findings on 10 lymphomas, each with translocations involving c-MYC and BCL2 or BCL6 and show that these cases frequently showed a common immunophenotype that includes decreased expression of CD20. Because these lymphomas often show aggressive biologic behavior and poor clinical outcome, recognition of this relatively common immunophenotype may be useful for identifying cases for confirmatory cytogenetic studies, as often, flow cytometry provides the first assessment of these clinical specimens.
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PMID:"Double-Hit" mature B-cell lymphomas show a common immunophenotype by flow cytometry that includes decreased CD20 expression. 2141 90


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