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Query: UMLS:C0079731 (B-cell lymphoma)
 16,671 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chromosomal translocation involving the BCL6 gene affects not only immunoglobulin (Ig) genes but also a number of non-Ig genes as partners. The molecular anatomy of the BCL6 gene rearrangements in 39 cases with diffuse large B-cell lymphoma (DLBCL) by long-distance polymerase chain reaction-based assays was determined. The results showed that Ig genes were affected in 21 cases; non-Ig genes, 15 cases; a deletion of more than a 1-kb segment, 2 cases; and a point mutation, 1 case. Comparative studies between the 21 cases with Ig gene partners and the 17 cases with non-Ig gene partners, including 2 cases with the deletion, showed that the overall survival of the latter group of patients was significantly inferior to that of the former (P = .0440), and the estimated 2-year overall survival rates were 58.3% vs 17.6% (P = .005). Non-Ig/BCL6 fusion is a poor prognostic indicator of DLBCL, and DLBCL with BCL6 translocation could be subclassified according to the individual partner locus and/or gene. (Blood. 2000;96:2907-2909)
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PMID:Nonimmunoglobulin (non-Ig)/BCL6 gene fusion in diffuse large B-cell lymphoma results in worse prognosis than Ig/BCL6. 1102 30

Studies of lymphoid neoplasms occurring in normal or genetically engineered mice have revealed parallels and differences to non-Hodgkin lymphomas (NHL) of humans. Some mouse lymphomas have strong histologic similarities to the human NHL subsets including precursor B- and T-cell lymphoblastic, small lymphocytic, splenic marginal zone, and diffuse large-cell B-cell lymphomas (DLCL); whether molecular parallels also exist is under study. Others mouse types such as sIg+ lymphoblastic B-cell lymphoma have no histologic equivalent in human NHL even though they share molecular deregulation of BCL6 with human DLCL. Finally, Burkitt lymphoma does not appear to occur naturally in mice, but it can be induced with appropriately engineered transgenes.
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PMID:Non-Hodgkin lymphomas of mice. 1135 82

To detect immunoglobulin heavy chain (IGH) gene translocations with specific oncogene loci, we established an interphase cytogenetic approach using double-color fluorescence in situ hybridization (DC-FISH), which we used to analyze 173 patients with B-cell lymphoma. DC-FISH using the IGH gene (14q32.3) in combination with c-MYC (8q24.1), BCL1 (11q13.3), BCL2 (18q21.3), BCL6 (3q27), and PAX-5 (9p13) gene probes detected IGH translocations in 70 (40.5%) of 173 patients. The partner genes involved in IGH translocations were identified in 56 (80%) of 70 patients, and fusion of the IGH gene with specific oncogenes was detected in 53 of 56 patients, particularly in interphase nuclei of 28 patients for whom cytogenetic analysis was not informative. The most common partner gene was BCL2 (19 patients; 27% of IGH translocation-positive patients), followed by BCL6 (16; 23%), BCL1 (11; 16%), c-MYC (7; 10%), and PAX-5 (2; 3%). These oncogenes were closely associated with subtypes of B-cell lymphoma. The other partners were 19q13 (BCL3), 6p25 (MUM1/IRF4), 1q36, and chromosome 8 identified in one patient each. Six of the nine patients with add(14)(q32) showed a BCL6/IGH translocation. Double translocations of the IGH gene were found in three patients; c-MYC+BCL1, c-MYC+BCL2, and c-MYC+BCL6 in each one. Interphase FISH using specific IGH-translocation probes is valuable for defining clinically meaningful subgroups of B-cell lymphoma.
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PMID:Interphase detection of immunoglobulin heavy chain gene translocations with specific oncogene loci in 173 patients with B-cell lymphoma. 1152 May 58

The purpose of this study was to investigate the prognostic implications of BCL6 rearrangement in a uniformly treated population of patients with diffuse large B-cell lymphoma (DLBCL) and to characterise the relationship between BCL6 rearrangement and prognostic factors. A total of 269 patients with DLBCL entered a randomised trial comparing the chemotherapy regimen CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) to the MACOP-B (methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, bleomycin) regimen. In 44 cases, frozen tissue was available for assessment of BCL6 status by Southern blot analysis. BCL6 was rearranged in six of 43 evaluable cases (14%), and was associated with elevated lactate dehydrogenase (LDH), and a higher patient age. No association between BCL6 status and expression of BCL2, Ki-67 or TP53 was found. Patients presenting with BCL6 rearrangement displayed a weak trend towards better overall and failure-free survival (67 and 67% at 5 years), compared to patients with germline BCL6 (63 and 52%), but the difference was not statistically significant. In accordance with previously published series, the presence of BCL6 rearrangement does not define a prognostically distinct subgroup of DLBCL. Assessment of BCL6 status may, however, be of clinical interest when related to other prognostic variables.
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PMID:Prognostic implications of BCL6 rearrangement in uniformly treated patients with diffuse large B-cell lymphoma--a Nordic Lymphoma Group study. 1174 58

Low-grade marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type can transform into high-grade diffuse large B-cell lymphoma (DLBCL). Up to 60% of the MALT lymphomas contain the recently described t(11;18). However, this translocation has not been detected in any DLBCL so far. To elucidate the pathogenesis of these tumors, microsatellite screening of 24 gastric MALT lymphomas was performed and the results were compared with aberrations detected in a previous study on gastric DLBCL. The most frequent aberration, found in 21% of the MALT lymphomas that were exclusively t(11;18)-negative cases, was amplification of the 3q26.2-27 region (harboring the locus of the BCL6 gene). Allelic imbalances in regions 3q26.2-27, 6q23.3-25, 7q31, 11q23-24, and 18q21 were shared by both MALT lymphoma and DLBCL. Loss of heterozygosity in regions 5q21 (APC gene locus), 9p21 (INK4A/ARF), 13q14 (RB), and 17p13 (p53) and allelic imbalances in 2p16, 6p23, and 12p12-13 occurred exclusively in DLBCL. Only one of 10 t(11;18)-positive MALT lymphomas showed an additional clonal abnormality. These tumors thus display features of a clonal proliferation characterized by the presence of the t(11;18). However, they only rarely display secondary aberrations and do not seem to transform into DLBCL. In contrast, t(11;18)-negative MALT lymphomas show numerous allelic imbalances--some of them identical with aberrations seen in DLBCL--suggesting that this group is the source of tumors eventually transforming into high-grade DLBCL.
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PMID:Gastric marginal zone B-cell lymphomas of MALT type develop along 2 distinct pathogenetic pathways. 1213 Apr 78

To address the possible genetic relationship between primary mediastinal large-B-cell lymphoma (PMLBCL) and diffuse large-B-cell lymphoma (DLBCL), we compared DNA copy number changes identified by comparative genomic hybridization (CGH) analysis of 40 PMLBCL and 91 DLBCL tumors. We assessed their karyotypes by G-banding; amplification of MYC, BCL2, and REL genes by Southern blotting; and incidence of nonpolymorphic BCL6 mutations by single-strand conformation polymorphism analysis (SSCP). Overall, CGH identified overlapping and nonoverlapping patterns of DNA copy number changes in the two groups. Among the latter changes, gains of chromosomes 8, 11, 15, and 16 and losses of chromosomes 5, 10, 15, 16, 17, and 20 were seen only in DLBCL, and gains of chromosomes 10, 21, and 22 and losses of chromosomes 11, 13, and 18 were seen only in PMLBCL. Several overlapping changes were identified in both groups, with variation in incidence. Statistical analysis of these changes showed significant gains of chromosomes 3 (P <or= 0.05) and 7q (P <or= 0.05) in DLBCL and gains of chromosomes 9 (P <or= 0.05) and 19 (P <or= 0.05) and the X chromosome (P <or= 0.05) and loss of chromosome 4 (P <or= 0.05) in PMLBCL. Frequent recurring DNA amplification at 2p13-15 and less frequent amplification at 6p21, 12q13, and 18q21 were noted in both groups. Recurring amplification at 1q21 was seen only in DLBCL, whereas nonrecurring amplification at 10p11.2 and 15q22-24 was seen only in PMLBCL. G-banded karyotype analysis identified t(3;14)(q27;q32) in one and t(14;18)(q32;q21) in two cases of PMLBCL. Seven of 13 cases exhibited SSCP variants in the 5' noncoding region of BCL6. In addition, 19 of 24 PMLBCLs assayed for BCL6 protein expression by immunohistochemistry showed positive results, indicating an origin from a germinal center (GC)-derived B cell. Based on these data, we conclude that PMLBCL is a distinct entity among GC-derived high-grade DLBCLs.
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PMID:Similar patterns of genomic alterations characterize primary mediastinal large-B-cell lymphoma and diffuse large-B-cell lymphoma. 1179 37

BCL6 translocation affecting the chromosomal band 3q27 can involve a number of non-immunoglobulin (non-IG) gene loci as partners. We report here that the gene for interleukin-21 receptor (IL-21R) is the partner of BCL6 in t(3;16)(q27;p11) translocation. The two breakpoints on 16p11 of a lymphoma cell line YM and case no. 1012 with diffuse large B-cell lymphoma, both of which carried t(3;16), were localized within the 27-kb intron 1 of IL-21R. As a result of t(3;16), the promoter region of IL-21R was substituted for the regulatory sequences of BCL6 in the same transcriptional orientation. Reverse transcriptase-mediated polymerase chain reaction revealed chimeric mRNA consisting of two non-coding exons 1a/1b of IL-21R and coding exons of BCL6 in both lymphoma cells. Fluorescence in situ chromosomal hybridization of YM metaphase cells revealed fusion signals that contained both the BCL6 and IL-21R sequences on the der(3)t(3;16) chromosome. IL-21R was actively transcribed in YM cells, while BCL6 that was under the control of the IL-21R promoter was only moderately expressed at the mRNA and protein level. We constructed expression plasmid of BCL6 that followed the promoter sequences of IL-21R. COS-7 cells transiently transfected with the plasmid expressed high level Bcl-6 protein and displayed nuclear staining with a characteristic punctate pattern by immunofluorescence, indicating that expression of BCL6 can be enhanced by t(3;16). This study added to the list of non-IG partners of BCL6 translocations a new class of gene, i.e. cytokine receptor gene, the expression of which is closely associated with lymphoid cells.
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PMID:The gene for interleukin-21 receptor is the partner of BCL6 in t(3;16)(q27;p11), which is recurrently observed in diffuse large B-cell lymphoma. 1182 49

BCL6 is a member of the POZ/zinc finger (POK) family involved in survival and/or differentiation of a number of cell types and in B cell lymphoma upon chromosomal alteration. Transcriptional repression by BCL6 is thought to be achieved in part by recruiting a repressor complex containing two class I histone deacetylases (HDACs). In this study we investigated whether BCL6 could also target members of class II HDACs. Our results indicate that three related class II deacetylases, HDAC4, HDAC5, and HDAC7 can associate with BCL6 in vivo and in vitro. Using electron microscopy, we found that endogenous BCL6 and class II HDACs partially co-localize in the nucleus. Overexpression experiments showed that BCL6 and HDAC4, -5, or -7 are intermingled onto common nuclear substructures and form stable complexes. A highly conserved domain in the N-terminal region of HDAC5 and HDAC7 as well as the zinc finger region of BCL6 were found necessary for the complex formation in vivo and in vitro. Moreover, our data point to the zinc finger region of BCL6 as a multifunctional domain which, beside its known capacity to bind DNA, is involved in the nuclear targeting of the protein and in the recruitment of the class II HDACs, and hence constitutes an autonomous repressor domain. Since PLZF, a BCL6 relative, could also interact with HDAC4, -5, and 7, we suggest that class II HDACs are largely involved in the control of the POK transcription factors activity.
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PMID:Class II histone deacetylases are directly recruited by BCL6 transcriptional repressor. 1192 73

Methionine aminopeptidase type 2 (MetAP2) is a bifunctional protein that plays critical roles in the regulation of protein synthesis and post-translational processing by (a) protecting the alpha subunit of eukaryotic initiation factor 2 from inhibitory phosphorylation by eukaryotic initiation factor 2 kinases and (b) removing the amino-terminal methionine residue from nascent protein. MetAP2 is also known as the molecular target of the angiogenesis inhibitor TNP-470. In addition, it has been recently suggested that MetAP2 has an antiapoptotic function in mesothelioma. To know the pattern of expression of MetAP2 in normal and neoplastic tissues, we raised two specific rabbit polyclonal Abs and examined the pattern of MetAP2 expression in various normal and pathologic specimens. Unexpectedly, we found a very high and selective expression of MetAP2 in germinal center B cells. In the germinal center, dark zone B cells tended to express more MetAP2 than light zone B cells. When 200 malignant lymphomas of various subtypes were studied, a high level of MetAP2 expression, equivalent to that observed in germinal center B cells, was noted exclusively on B-cell lymphoma subtypes that are currently regarded as the neoplastic counterparts of germinal center B cells. The expression of MetAP2 in diffuse large B-cell lymphomas correlated well with that of BCL6 (p < 0.05) but not with that of either CD10 or BCL2. These data suggest that MetAP2 has specific function(s) in germinal center B cells and that the function is shared by neoplastic counterparts of germinal center B cells.
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PMID:High expression of methionine aminopeptidase type 2 in germinal center B cells and their neoplastic counterparts. 1211 91

Diagnostically primary central nervous system lymphomas (PCNSL) have to be differentiated from glioblastoma and brain metastases. Histologically the overwhelming majority of PCNSL is represented by diffuse large B-cell lymphomas, in this series with a BCL6 expression in 80% of the cases detected by immunohistochemistry. Stereotactic biopsy is the method of choice in establishing the definite diagnosis and intraoperative smear cytology will detect the lymphoid blasts. To confirm the B-cell lineage, immunohistochemistry is needed (CD20, CD79a). Small reactive T-lymphocytes and monohistiocytic cells and activated "microglia" are found within and at the periphery of PCNSL foci. The infiltrated brain tissue shows partially pleomorphic reactive astrocytes that can be confused with neoplastic astrocytes, especially in small specimens. In contrast to high-grade gliomas, however, PCNSLs do not show endothelial proliferations. Subtypes or variants of diffuse large B-cell lymphomas can also be observed in cases of PCNSL: the anaplastic variant with large multinucleated tumour cells resembling Reed-Sternberg cells, T-cell rich B-cell lymphoma and intravascular B-cell lymphoma with primary manifestation within the brain or the spinal cord. HIV/AIDS-associated PCNSLs are characterised by large plasmoblastic or small Burkitt-like cells and tumour necrosis. Primary leptomeningeal large B-cell lymphomas do occur very rarely and are diagnosed by cerebrospinal fluid cytology.
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PMID:[Primary CNS lymphomas. Morphology and diagnosis]. 1218 81


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