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 chromosome 11q13 bcl-1 locus is rearranged in the majority of centrocytic lymphomas, a CD5-positive B-cell non-Hodgkins lymphoma, as a result of reciprocal translocation with the 14q32 immunoglobulin heavy chain genes. Although several 11q13 bcl-1 breakpoint sites have been characterized, a postulated bcl-1 oncogene was not identified. Recently, however, a gene encoding cyclin D1, designated PRAD1, was proposed as a candidate bcl-1 oncogene; accumulated evidence now indicates this gene is bcl-1. To further characterize 11q13 breakpoints in B-cell neoplasms, we analyzed 26 centrocytic lymphomas and 68 other B-cell cancers by Southern blot using a panel of breakpoint probes spanning 110 kilobases of the bcl-1 and PRAD1 loci. Nineteen centrocytic cases (73%) showed rearrangement, 15 at bcl-1 breakpoint sites and 5 at PRAD1 sites. One case was rearranged at both bcl-1 and PRAD1 loci. All but the latter case showed comigration of rearranged bcl-1 or PRAD1 bands and immunoglobulin heavy chain joining gene bands, consistent with the t(11;14). bcl-1 rearrangement was present in only one of 68 noncentrocytic B-cell neoplasms; none showed PRAD1 rearrangement. Thus, bcl-1 and PRAD1 rearrangement is strongly associated with centrocytic lymphoma, providing a useful molecular marker for classifying this subtype of lymphoma and suggesting an important role for PRAD1 cyclin D1 in the pathogenesis of this neoplasm.
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PMID:Characterization of chromosome 11 translocation breakpoints at the bcl-1 and PRAD1 loci in centrocytic lymphoma. 139 69

Recent immunopathologic studies have demonstrated that primary follicles and the mantle zones of secondary follicles are composed largely of virgin B lymphocytes which migrate from the bone marrow to these areas, and are the precursor cells of germinal centers. Non-Hodgkin's lymphomas corresponding to these immature B cells include mantle zone lymphoma (MZL), a primary follicle variant of MZL without reactive germinal centers, and diffuse intermediate lymphocytic (centrocytic) lymphoma. Diffuse intermediate lymphocytic lymphoma (DILL) is considered a late stage in the progression of MZL. Cytologically, these lymphomas usually resemble their normal cellular counterparts and consist predominantly of atypical small lymphoid cells with slightly-irregular and indented nuclei, moderately-coarse chromatin, inconspicuous nucleoli, and scant cytoplasm. Small lymphocytic, cerebriform and blastic variants have also been described. In smears and touch preparations, the neoplastic cells are usually prolymphocytes. Immunologically, the cells have features of virgin B cells, bearing pan-B cell antigens along with monoclonal surface IgM, with or without surface IgD, and CD5 (Leu 1) antigen, and lacking common acute lymphocytic leukemia associated (CALLA) antigen. Cytogenetically, the t(11;14)(q13;q32) has been associated with this group of lymphomas, and expression of the putative cellular oncogene bcl-1 (11q13) has been demonstrated in 30-50% of cases. Clinically, the patients have a median age of 60 years and usually present with advanced stage disease. Splenomegaly, often massive, is present in 80% of those with MZL. Patients with MZL have a significantly longer median survival (74-77 months) than those with DILL (30-33 months), and survival in both groups is significantly prolonged if a complete clinical remission is attained. Based on clinical studies, MZL should be considered a low grade lymphoma and DILL should be considered an intermediate grade lymphoma by Working Formulation criteria. The lymphomas of primary follicle/mantle zone origin are a distinct clinicopathologic entity biologically analogous to the follicular and diffuse lymphomas of germinal center origin, from which they should be distinguished in current and future classifications of non-Hodgkin's lymphoma.
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PMID:Non-Hodgkin's lymphomas of primary follicle/mantle zone origin. 171 36

The authors investigated the structural organization of the bcl-1 locus, a putative oncogene associated with reciprocal chromosomal translocation t(11;14), by Southern blot hybridization analysis and its frequency, distribution, and prognostic significance in a panel of 156 clinically and pathologically well-defined B-cell chronic lymphocytic leukemias (CLLs) and non-Hodgkin's lymphomas (NHLs). The authors detected bcl-1 rearrangements in only 2 of 42 CLLs and 4 of 114 NHLs, specifically 3 of 29 diffuse small lymphocytic and 1 of 10 diffuse small cleaved cell and none of 5 diffuse intermediate lymphocytic, 13 follicular predominantly small cleaved, 17 follicular mixed small cleaved and large cell, 4 diffuse mixed small and large cell, 26 diffuse large cell, and 10 diffuse small noncleaved cell lymphomas. None of seven cases of Rai stage III or IV CLL or seven diffuse large cell lymphomas occurring as Richter's syndrome exhibited bcl-1 rearrangements. In conclusion, the bcl-1 locus rearranges in only about 4% of B-cell CLLs and NHLs, is predominantly rearranged in low-grade B-cell neoplasms, and does not appear to be preferentially associated with those occasional CLLs and low-grade NHLs displaying clinical aggressiveness, advanced clinical stage, or large cell transformation (Richter's syndrome). Therefore the demonstration of bcl-1 rearrangement does not appear to have clinically useful prognostic significance.
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PMID:bcl-1 rearrangement. Frequency and clinical significance among B-cell chronic lymphocytic leukemias and non-Hodgkin's lymphomas. 190 Mar 88

Nine patients with t(11;14) and B non-Hodgkin's lymphomas composed of small to intermediately sized cells with irregular nuclei are described. Immunophenotyping was performed on seven cases, which were M+, D- with light chain restriction, CD5+, CD10-, and CD20+, suggesting that they were non-follicle centre cell lymphomas. The translocation (11;14) (in three cases the only cytogenetic anomaly) was associated with rearrangement of bcl-1 in four of the five cases investigated. Translocation (11;14) has been described in an apparently heterogeneous group of low-grade lymphoid malignancies which we suggest have a non-follicle centre cell lineage in common. This translocation may be associated with these lymphomas in the same way that t(14;18) is associated with follicle centre cell lymphomas.
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PMID:Translocation (11;14): a cytogenetic anomaly associated with B-cell lymphomas of non-follicle centre cell lineage. 200 19

Thirty-two extranodal lymphomas of the gastrointestinal (GI) tract underwent molecular genetic analysis by Southern blotting using probes for the immunoglobulin genes and the bcl-1, bcl-2, and c-myc loci, commonly involved in lymphomagenesis. No bcl-1 rearrangements were found. There was only one large-cell lymphoma with a bcl-2 rearrangement. A rearrangement of the c-myc gene was found in six of eight Burkittlike lymphomas of the intestine. In five of these six cases, a chromosomal translocation t(8;14) with an unusual breakpoint was demonstrated by comigration of the rearranged c-myc and a rearranged JH sequence. This pattern of rearrangement has not been previously associated with a specific group of non-Hodgkin's lymphomas. In contrast to all six low-grade lymphomas, c-myc rearrangements were found in 6 of 12 large-cell or high-grade mucosa-associated lymphomas of the stomach. No comigration of c-myc and immunoglobulin heavy-chain gene sequences were found. We conclude that primary GI lymphomas have different molecular genetic characteristics compared with node-based follicle center-cell lymphoma and as a group are not related to these lymphomas. In addition, the prevalence and patterns of c-myc rearrangements in the gastric large-cell lymphomas and ileocecal Burkittlike lymphomas are noteworthy and suggest a different and distinct pathogenesis for these tumors.
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PMID:Molecular genetics of gastrointestinal non-Hodgkin's lymphomas: unusual prevalence and pattern of c-myc rearrangements in aggressive lymphomas. 220 May 38

Immunohistochemical expression of PRAD1/cyclin D1 protein has been investigated in 106 tissue specimens of 104 cases of lymphoma, non-neoplastic lymphoid disorders and other hematologic malignancies by employing the monoclonal antibody 5D4 with formalin-fixed paraffin-embedded sections, using the microwave oven heating method. Positive neoplastic cells were found in 60 (74%) of 81 cases of non-Hodgkin's lymphoma. The positivity pattern was nuclear in 17 (85%) of 20 cases of mantle cell lymphoma in which cytoplasmic staining was also seen. This pattern of cyclin D1 positivity was in contrast to the negative staining of normal reactive mantle zones. In the other cases, positivity appeared to lie within the cell cytoplasm without nuclear staining, and most of the nodal follicular and diffuse B-cell lymphomas variously expressed PRAD1/cyclin D1. In contrast, the reaction was absent in a significant number of T-cell and extranodal B-cell lymphomas. Immunolocalization of PRAD1/cyclin D1 expression appears to be a useful diagnostic adjunct to discriminate mantle cell lymphoma from other non-Hodgkin's lymphomas.
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PMID:Immunohistochemical analysis of cyclin D1 protein in hematopoietic neoplasms with special reference to mantle cell lymphoma. 753 81

Mantle cell lymphomas (MCLs) are typically CD5-expressing B-cell non-Hodgkin's lymphomas (NHLs) that frequently harbor the chromosomal translocation t(11;14) or bcl-1 gene rearrangements. Insufficient data are available on the biologic features and clinical behavior of rigorously characterized MCL. As these NHLs have been reported to exhibit various histologic and cytologic expressions, and in order to avoid using somewhat arbitrary and subjective morphologic definitions, we chose to study cases of MCL selected on more objective grounds. Specifically, 15 samples (from 14 patients) of CD5-expressing B-cell NHLs with detectable bcl-1 gene rearrangement were included. Overall, these patients had relatively uniform clinical manifestations. Most were older men (mean age, 67 years) who presented with lymphadenopathy, high-stage disease, and bone marrow involvement. All but two patients relapsed, demonstrated residual tumor, or had disease progression after an initial response to various therapies. Nine patients have died; these patients had a median survival of only 19 months. All cases could be classified within the broad morphologic spectrum previously described for MCL, and no predominant histologic subtype was observed. However, cases could be segregated into two major groups according to tissue architecture: one with a purely diffuse pattern and the other with at least a focal nodular component. Patients with purely diffuse tumors had a lower survival rate (0%) than those with tumors having a nodular component (62% survival rate). In contrast to the morphologic variability, these NHL exhibited a rather homogeneous immunophenotypic pattern. All cases demonstrated intense CD20 expression, with typically intense IgM and light chain expression, and relatively weak IgD expression. In no case was CD10 detected on the neoplastic cells. DNA content analysis showed aneuploidy only in three instances, and two groups of cases could be arbitrarily defined on the basis of their S-phase fraction. A relationship between a purely diffuse growth pattern and a high S-phase fraction (greater than 5%) was observed. As expected from this association, patients with tumors having high S-phase fractions fared worse (14% survival rate) than those patients with tumors showing lower S-phase fractions (57% survival rate). Thirteen NHLs from 12 patients had amplifiable bcl-1 gene rearrangements at the major translocation cluster (MTC). The bcl-1 breakpoints aggregated within a 63-bp region of the MTC, and the amplified tumor DNA from each patient had unique N-nucleotide junctional sequences and Ig joining region breakpoint sites.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:CD5-expressing B-cell non-Hodgkin's lymphomas with bcl-1 gene rearrangement have a relatively homogeneous immunophenotype and are associated with an overall poor prognosis. 753 38

Diffuse large B cell lymphomas (DLBLs) represent a heterogeneous collection of aggressive non-Hodgkin's lymphomas that can arise either de novo or as a result of transformation from chronic lymphocytic leukemia, small lymphocytic lymphoma, follicular lymphomas, or lymphomas of mucosa-associated lymphoid tissue. A small percentage of DLBLs express the CD5 antigen. The majority of these cases have evolved from a pre-existing low grade non-Hodgkin's lymphoma (Richter's syndrome). However, we identified and characterized nine CD5-positive DLBLs in which the patients did not have a previous history or concomitant evidence of chronic lymphocytic leukemia, small lymphocytic lymphoma, follicular lymphoma, or mucosa-associated lymphoid tissue-associated non-Hodgkin's lymphoma, suggesting that they arose de novo. All nine cases expressed CD20 and monotypic immunoglobulin, all eight cases examined expressed CD19, CD22 and CD43, eight of the nine cases expressed HLA-DR, and two of eight cases expressed CD11c. None of the cases expressed CD3, CD10, CD11b, CD21, CD23 or CD30. CD5 expression by these cells was found to be identical to that of CD5-positive B cell chronic lymphocytic leukemia by quantitative polymerase chain reaction analysis of CD5 mRNA. These nine de novo CD5-positive DLBLs exhibited clonal immunoglobulin heavy and light chain gene rearrangements but lacked integration of the Epstein-Barr virus genome and structural alterations of the bcl-1, bcl-2, c-myc, H-ras, K-ras, and N-ras proto-oncogenes and the p53 tumor suppressor gene. However, bcl-6 proto-oncogene rearrangement, which is involved in chromosome band 3q27 aberrations, was found in four cases (44.4%). This is comparable with the frequency of bcl-6 gene rearrangement in CD5-negative DLBL. In contrast, bcl-6 gene rearrangement was absent in six cases of DLBL associated with Richter's syndrome. These findings suggest that de novo CD5-positive DLBLs are genotypically similar to CD5-negative DLBLs and may be pathogenetically distinct from the DLBLs associated with Richter's syndrome.
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PMID:De novo CD5-positive and Richter's syndrome-associated diffuse large B cell lymphomas are genotypically distinct. 754 11

Among extranodal non-Hodgkin's lymphomas, primary cutaneous lymphomas (CLs) represent a consistent group of B- and T-cell malignancies. We investigated the arrangement of Ig and T-cell receptor (TCR) genes, together with the involvement of several oncogenes and the tumor-suppressor gene p53, in a panel of primary cutaneous B- and T-cell lymphomas (CBCLs and CTCLs). Southern blot analysis was performed to detect rearrangements of the Ig, c-myc, bcl-1, bcl-2, bcl-3, bcl-6, and the NFKB2/lyt-10 genes in 52 cases of CBCLs and of the TCR, bcl-3, and NFKB2/lyt-10 genes in 38 cases of CTCLs. tal-1 gene deletions were analyzed in CTCLs by means of polymerase chain reaction (PCR). p53 gene mutations were assayed using PCR, single-strand conformation polymorphism analysis, and direct DNA sequencing in CBCL and CTCL cases. Clonal rearrangements of Ig genes or oncogenes were found in 25 of the 52 CBCLs. In particular, we detected rearrangements of the bcl-1 locus (2 cases), the bcl-2 gene (2 cases), the NFKB2/lyt-10 gene (2 cases), and the bcl-6 gene (1 case); interestingly, 4 of these cases showed a germline arrangement of the Ig genes. Clonal rearrangements of TCR genes were detected in 37 of the 38 CTCLs. Rearrangements of the NFKB2/lyt-10 gene were present in 2 cases and tal-1 gene deletions in 3 CTCL cases; p53 gene mutations were detected in 1 CTCL case. Overall, our data indicate that (1) clonal rearrangement of Ig genes is frequently undetectable by means of Southern blot in CBCLs (60%); (2) genetic lesions are involved in a limited but significant fraction of primary CLs showing a molecular marker of clonality (13/62; 20%); and (3) rearrangements of the bcl-1, bcl-2, or bcl-6 loci, associated with specific subsets of nodal lymphoid neoplasias, are rarely observed in CBCLs. Moreover, our results suggest that tal-1 gene deletions may play a pathogenetic role in non-acute T-cell malignancies and that, in the context of lymphoid malignancies, CLs may represent a favorable target for the possible oncogenic potential of the NFKB2/lyt-10 gene.
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PMID:Molecular analysis of cutaneous B- and T-cell lymphomas. 757 11

Measurement of growth fraction is an important way to provide an objective assessment of non-Hodgkin's lymphomas; however, many of the techniques used require fresh tissue and/or special instrumentation. Recently, antibodies to the proliferating cell nuclear antigen (PCNA)/cyclin reactive in paraffin-embedded sections have become available. To investigate the utility of one such antibody in the study of follicular center cell (FCC) lymphomas and cleaved cell lymphomas of centrocytic type (CC), paraffin sections from 40 cases that had been characterized in two previous morphometric studies were stained with a PCNA antibody. Strong correlations were found between PCNA staining in formalin- and B5-fixed tissues, between the overall proportion of PCNA-positive cells and the proportion in the area of greatest staining, and between strong and total staining. Proliferating cell nuclear antigen staining was significantly stronger in the noncleaved FCC lymphomas than in the cleaved cell lymphomas. The FCC lymphomas showed moderate to strong correlations between PCNA staining and morphometric features of transformation, but only nuclear area correlated with PCNA staining in the CC group. Proliferating cell nuclear antigen staining was not significantly different between CC lymphomas with and without the characteristic bcl-1/PRAD 1 gene rearrangement. In summary, PCNA staining of either B5- or formalin-fixed, paraffin-embedded tissue sections is a simple aid in the objective categorization of FCC lymphomas and may offer additional potentially prognostic information in some FCC subsets and in CC lymphomas. The findings further support the distinction between CC and true FCC lymphomas.
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PMID:Growth fraction in centrocytic and follicular center cell lymphomas: assessment in paraffin sections with a proliferating cell nuclear antigen antibody and morphometric correlates. 768 24


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