Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:A9QXG9 (bcl-2)
 7,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

T-cell-rich B-cell lymphomas (TCRBCLs) are recently described, unusual non-Hodgkin's lymphomas that have a diffuse morphology, a predominance of reactive T-cells, and a minority of neoplastic B-cells. The clinical and pathological features of 19 TCRBCLs, all of which demonstrated B-cell clonality, are presented. These lymphomas generally affected older patients by widespread disease and usually were nodal in origin. Treatment varied, but continuous complete remissions (eight patients) were achieved only in those receiving chemotherapy directed at intermediate-grade lymphomas. Although morphologically heterogeneous, all cases resembled peripheral T-cell lymphomas (PTCLs); several TCRBCLs also contained Reed-Sternberg-like cells. Flow cytometry or frozen-section immunoperoxidase failed to detect monotypic immunoglobulin (Ig) in eight of eight cases tested. In contrast, paraffin immunoperoxidase was very useful diagnostically, showing large L26 (CD20-associated) positive cells scattered singly or in small clusters among numerous small T-cells (UCHL1[CD45RO] positive) in all cases. Monotypic cytoplasmic Ig was present in 16 of 19 cases, one of which exhibited plasmacytic differentiation. Southern blot analysis demonstrated relatively faint Ig JH and/or JK bands, indicating a small monoclonal B-cell population in nine of 11 cases, one of which also showed a bcl-2 rearrangement. No T-cell receptor gene rearrangements were observed. These results showed that TCRBCLs may be easily confused with PTCLs or occasionally confused with Hodgkin's disease. TCRBCLs are probably heterogeneous biologically; some cases are of follicular center cell origin. These lymphomas respond to chemotherapy directed at intermediate-grade lymphomas, apparently have a better prognosis than PTCLs, and seem to represent morphological variants of different types of large B-cell lymphomas.
 ...
PMID:T-cell-rich B-cell lymphomas. A clinicopathologic study of 19 cases. 816 40

Cytogenetic and molecular results in 10 patients with extranodal lymphoma (MALT): 5 low grade and 5 high grade, were compared with the results observed in nodal lymphomas. This study suggests that there are cytogenetic differences between extranodal and nodal low grade lymphomas. Both molecular analysis by conventional Southern blot with probes for the major and minor regions of bcl-2 gene, and PCR analysis with primers from these regions, showed that t (14; 18) is a sporadic event in MALT lymphomas.
 ...
PMID:[Cytogenetic and molecular aspects in MALT lymphomas]. 177 8

Large cell lymphomas (LCLs) are heterogeneous in morphology, clinical presentation, and behavior. We studied 52 de novo LCLs of B-cell type for rearrangements of the bcl-2 and c-myc oncogenes by Southern blot analysis and related these data to the primary site of presentation, stage, and cytomorphology. Thirteen tumors had comigrating rearrangements of JH and bcl-2, indicative of a t(14;18). Far more primary nodal lymphomas than extranodal lymphomas carried a t(14;18) (40% v less than 5%). Additionally, almost all lymphomas with a t(14;18) versus 41% of the tumors without a bcl-2 rearrangement presented with lymphadenopathy. c-myc rearrangements were seen in 35% of the extranodal lymphomas and 5% of the nodal lymphomas. No differences were observed in bone marrow involvement and staging according to Ann Arbor. bcl-2 rearrangements were found in 50% of the LCLs with cleaved nuclei, whereas c-myc rearrangements were relatively frequent (25%) in the noncleaved subtype. Our data support the hypothesis that primary nodal and extranodal lymphomas have a different genetic origin.
 ...
PMID:Essential differences in oncogene involvement between primary nodal and extranodal large cell lymphoma. 182 61

Chromosomal translocations involving the heavy chain immunoglobulin locus on chromosome 14 and a region on chromosome 18 encoding the bcl-2 gene [t(14;18)] are a characteristic and prevalent chromosomal abnormality in nodal malignant lymphoma, particularly follicular lymphoma. Using the polymerase chain reaction on routinely processed tissue, t(14;18) has been demonstrated in 22% of primary intestinal lymphomas, i.e. in two of nine cases of malignant lymphomatous polyposis, in four of 19 cases of polymorphic B-cell lymphoma and in one of four high-grade unclassified tumours. The findings in this study contradict those of other studies which have shown no such translocation in primary gastric and small intestinal lymphoma. The presence of t(14;18) indicates heterogeneity of molecular abnormalities within histopathologically homogeneous tumours and suggests that caution should be employed in using molecular cytogenetic data to support theories of tumour histogenesis. The low prevalence of this translocation in intestinal lymphoma makes the use of such a methodology as a primary diagnostic aid doubtful, although the technique may help to distinguish primary and secondary lymphoma and could also be used to demonstrate secondary spread.
 ...
PMID:14;18 translocation in primary intestinal lymphoma: detection by polymerase chain reaction in routinely processed tissue. 190 95

High-grade B-cell lymphomas, whether originated in a lymph node or in mucosa-associated lymphoid tissue (MALT), show similar morphologic traits, a fact that has fueled a long-running controversy about whether they represent different entities. They differ, however, in that some high-grade MALT lymphomas show less aggressive clinical behavior, a focal low-grade component being identified in some of them. In a search for bcl-2 protein expression, we have found a significant difference between nodal (39/48) and MALT high-grade B-cell lymphoma (1/15) (P less than 0.01). Bcl-2 gene product is an inner mitochondrial membrane protein able to give a survival advantage to B-cell lines by blocking programmed cell death. This protein is usually expressed by memory or resting B cells, most activated B cells being bcl-2 negative, except in lymph-node-originated high-grade B-cell lymphomas, which appear to be mainly bcl-2 positive. Presence of bcl-2 protein in nodal large-cell lymphomas seems to be independent of a t(14;18) translocation, only being found in 19 to 28% of these lymphomas, although it constitutes a definite difference between both tumors, suggesting the existence of different molecular genetic characteristics and pathogenesis, and is possibly related to the more aggressive clinical behavior of nodal high-grade tumors.
 ...
PMID:Different bcl-2 protein expression in high-grade B-cell lymphomas derived from lymph node or mucosa-associated lymphoid tissue. 195 37

Nonrandom chromosomal translocations like the t(14;18), t(8;14), and t(11;14) are found in distinct types of B-cell malignancies. Recent molecular studies concerning their structure and origin showed that many translocations occur in early precursor B cells and may be interpreted as aberrant immunoglobulin gene rearrangements. The available data from in vitro experiments, transgenic mice, and normal human individuals indicate that these translocations are essential but insufficient for full tumorigenesis. The consequent "multi-hit" concept might have important implications for the detection of minimal residual disease using the polymerase chain reaction for these translocations. The strong associations with specific types of lymphomas underline their differences in histogenetic origin. Thus, based on differences in bcl-1 and bcl-2 rearrangements, molecular analysis may help to distinguish follicular lymphoma from diffuse centrocytic lymphoma and chronic lymphocytic leukemia. Furthermore, based on differences in bcl-2 and c-myc rearrangements, subtypes of de novo centroblastic lymphoma can be distinguished that have striking differences in biological behavior, especially nodal versus extranodal presentation. Therefore, future studies will show an increasing clinical relevance of molecular analysis in B-cell neoplasia.
 ...
PMID:The molecular biology of B-cell lymphoma: clinicopathologic implications. 203 77

Using three chromosome 18-specific DNAs, rearrangements of a bcl-2 gene were detected in 20 (44%) of 45 Japanese patients (pts) with follicular lymphoma (FL) and 3 (8%) of 36 pts with diffuse large cell lymphoma. The 21 pts had t (IgH; bcl-2), and of the remaining two who did not display it, one had chromosome t(14; 18). Compared with the findings in American pts, the lower frequency of t(14; 18)-positive lymphoma could reflect a difference in the incidence of overall nodal B lymphoma between Japan and the United States. 11 of 18 pts with t(14; 18)-positive FL expressed CD10 antigen on the cell surface and all 12 pts with t(14; 18)-negative FL did not, and the difference is statistically significant, indicating that t(14; 18)-positive Japanese FL is the same disease entity as most of American FL. Extra 18q- chromosome found in the advanced grade diseases of t(14; 18)-positive lymphoma results in amplification of the rearranged bcl-2 gene on 18q-, suggesting that the change is closely associated with transformation of FL carrying t(14; 18). It is thus possible of international realization to institute the prognostic factors and the treatment strategy for conquering t(14; 18)-positive lymphoma.
 ...
PMID:[bcl-2 gene involved in Japanese follicular lymphoma]. 220 16

Consecutive 431 patients with B-cell lymphoma seen in Aichi Cancer Center Hospital from 1964 to 1988 were analysed. Median age was 56 yr (range 8-86). There were 76 patients (17.6%) with follicular lymphoma and 355 with diffuse lymphoma. Among the 30 patients with follicular lymphoma, 10 (33%) were found to have a bcl-2 rearrangement. The incidence was lower than those reported in the United States. This might contribute to the lower incidence of follicular lymphoma cases in Japan. There were 168 patients (39.0%) with nodal lymphoma and 263 with extranodal lymphoma. Eight-four cases arose from the stomach, 84 from Waldeyer's ring, 21 small intestine and 13 thyroid. The distributions of extranodal B-cell lymphoma differed from those of T-cell lymphoma. Patients with gastric lymphomas in stage I were treated with resection alone. In the same manner, patients with Waldeyer's ring lymphoma in stage I were treated with radiotherapy alone. More than 90% of these patients were expected to survive without relapse. On the other hand, only 55% of patients with nodal lymphoma in stage I were expected to survive for more than 10 years. These findings suggest the site of localized lymphoma is an important determinant of outcome of clinical behavior.
 ...
PMID:[Characteristics of B-cell lymphoma in Japan]. 239 5

Fourteen cases of primary cutaneous B-cell lymphomas were investigated at the immunohistochemical and molecular level to further characterize this newly defined entity. Neoplastic cells from all cases, phenotyped with a panel of monoclonal antibodies, were positive for HLA-DR, for the B-cell markers CD19, CD22, but not CD23 (except one case), and negative for the T-cell marker CD2. Monoclonal immunoglobulin light chains were demonstrated in six cases. The reactivity with the Ki-67 monoclonal antibody indicated that the neoplastic cells are proliferating. In five biopsies the presence of dendritic cells infiltrating the neoplastic areas was revealed using the monoclonal antibody Kim4b. By Southern blot analysis, clonal rearrangement of the immunoglobulin heavy chain gene (involving one or both alleles) was shown in 12 of 14 cases and of the light chain genes in 13 cases. The bcl-2 oncogene, normally involved in nodal follicular lymphomas, was in germ-line configuration. The c-myc and the beta and gamma chain genes of the T-cell receptor were also in the germ-line configuration. None of the cases presented Epstein-Barr virus sequences. These data indicate that primary cutaneous lymphomas of B-cell origin share morphological and phenotypic similarities with the nodal B-cell lymphomas of follicular histotype, are proliferating, and express in 45% of cases clear monoclonal immunoglobulin light chain; the molecular analysis confirms the B-cell derivation and the monoclonal nature of this neoplasia; it also shows that neither bcl-2 nor c-myc oncogenes are involved and that no inappropriate rearrangements of the T-cell receptor genes are found in this lymphoma.
 ...
PMID:Clonal immunoglobulin gene rearrangements and normal T-cell receptor, bcl-2, and c-myc genes in primary cutaneous B-cell lymphomas. 250 46

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.
 ...
PMID:Molecular analysis of cutaneous B- and T-cell lymphomas. 757 11


1 2 3 4 5 6 7 8 9 10 Next >>