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

Recurrent chromosomal translocations in malignant lymphomas most commonly involve 18q21(bcl-2), 8q24 (c-myc) and 3q27 (bcl-6), with an incidence of 27%, 11% and 6%, respectively. Individual cases concurrently harbouring two of these three rearrangements have been previously reported. This report describes four patients with cytogenetic alterations affecting all three loci, which was confirmed by molecular analysis in one case. Clinically, each patient had aggressive B-cell lymphoma with disseminated disease often involving the central nervous system, poor response to chemotherapy and short survival. Activation of c-myc in association with deregulation of bcl-2, bcl-6 or both confers high-grade disease with a poor prognosis.
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PMID:Concurrent chromosomal alterations at 3q27, 8q24 and 18q21 in B-cell lymphomas. 1023 17

Marginal zone lymphoma (MZL) is a distinct entity among B-cell lymphomas. We report on a 53-year-old woman who developed disseminated primary cutaneous MZL with secondary lymph node involvement and perinodular spreading. The tumor cell phenotype was characterized as CD20/CD79a/kappa/lambda+/ bcl-2-positive, CD3/5/15/39/bcl-1-negative. Ki-67 was expressed by 20-35% of tumor cells. There was no evidence of systemic (including bone marrow) involvement. The diagnosis of MZL with plasmacellular differentiation (Stage IVa) was made. The patient was treated with interferon alpha2a injected s.c. at 9x10(6) U 3 days a week for 1 year. During this time the skin lesions completely disappeared. No evidence of lymph node or extracutaneous disease was found. The patient remains in complete remission. Side effects were only of grade I (WHO); the Karnovsky index was 90%. As shown for other types of primary cutaneous B-cell lymphoma, prolonged interferon alpha monotherapy may be effective in controlling the disease and/or inducing complete remission in MZL.
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PMID:Primary cutaneous marginal center lymphoma - complete remission induced by interferon alpha2a. 1035 36

The bcl-2 gene on chromosome 18 at q21 and the bcl-6 gene on chromosome 3 at q27 are both highly regulated during B-cell differentiation and show an inverse relationship of expression in the normal secondary lymphoid follicle. The objective of this study was to investigate the relationship between bcl-2 and bcl-6 protein expression and the relationship between protein expression and the corresponding chromosomal alterations in malignant lymphomas, including those associated with the germinal center. Expression of bcl-2 and bcl-6 proteins was studied in 55 cases of diffuse large B-cell lymphoma (DLBCL) and 21 cases of follicular lymphoma (FL), and the results correlated with the presence of t(14;18) and 3q27 abnormalities in a subset of 52 cases with cytogenetic analysis. These cases were selected to represent a spectrum of nodal and extranodal lymphomas, including those with and without a t(14;18). It was shown that the neoplastic cells in 71% of DLBCLs and 100% of FLs expressed bcl-6 protein. Expression of bcl-6 was seen more frequently in diffuse large B-cell lymphomas with large noncleaved morphology compared with immunoblastic morphology (82% v 27%, P = .0015), but failed to correlate with 3q27 abnormalities. Thirty-eight percent of cases with 3q27 abnormalities were bcl-6 protein negative, whereas 85% of cases without a 3q27 abnormalities were bcl-6 protein positive. Expression of bcl-2 protein was shown in 51% DLBCLs (nodal v extranodal, 71% v 30%, P = .012). bcl-2 protein was expressed in 89% of FLs with t(14;18), in contrast to 25% of FLs without t(14;18) (P = .016). In DLBCL and FL with t(14;18), the most common pattern of expression was bcl-2+/bcl-6+. In lymphomas without t(14;18), there was not an inverse relationship between bcl-2 and bcl-6 protein expression. In conclusion, these data suggest that mechanisms other than gene rearrangements can deregulate bcl-2 and bcl-6 expression in lymphomas, and there does not appear to be an inverse relationship between these two proteins as seen in the normal germinal center.
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PMID:Bcl-6 and Bcl-2 protein expression in diffuse large B-cell lymphoma and follicular lymphoma: correlation with 3q27 and 18q21 chromosomal abnormalities. 1041 99

The expression of the natural killer (NK) cell antigen, CD56, in hematological malignancies is rare. However, there are several reports that some hematological malignancies, such as T/NK cell lymphoma, multiple myeloma (MM) and acute myeloid leukemia (AML), express this molecule. In B cell non-Hodgkin's lymphomas (NHL), however, very limited number of cases have been reported to express CD56 molecule. Although one study has recently described that half of microvillous B cell lymphoma (MVL), an uncommon subset of large cell lymphoma, expressed CD56, there have been no reports about most common type of B-NHL, diffuse large B cell lymphoma (DLBL) other than a mention of weak CD56 expression in one of 83 DLBL. We herein presented the first case of diffuse large B cell lymphoma expressing CD56 clearly. The immunophenotype determined by immunostaining and flow cytometric analysis was CD10+, CD19+, CD20+, CD45RO-, CD3- and CD56+. On immunohistochemical study, neither bcl-2 nor TIA-1 was positive for tumor cell. Monoclonal immunoglobulin heavy chain (IgH) gene rearrangement was detected, and the sequence analysis of the variable region of IgH (VH) suggested that this tumor was derived from antigen selected post germinal center B cell. Conventional combination chemotherapy (CHOP) was administered, and the patient has still been in complete remission for 10 months.
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PMID:Diffuse large B cell lymphoma expressing the natural killer cell marker CD56. 1050 45

Primary mediastinal B-cell lymphoma (PMBL) shows chromosome 9p anomalies in 50% of cases. Based on reports that p16INK4A gene, located on this chromosomal arm, is frequently altered in aggressive lymphomas, we analysed for alterations of this gene in 27 cases of PMBL, which were part of a series of 32 PMBL cases that have been characterized for alterations in c-myc, p53, N-ras, bcl-1, bcl-2, bcl-6 and for Epstein-Barr virus (EBV) infection. Four cases showed p16INK4A gene anomalies, including three with promoter methylation and one homozygous deletion. Eight PMBLs showed c-myc rearrangements. Three additional cases showed sequence variations in the c-myc P2 promoter, two of which consisted of the same germline variation involving a novel polymorphic XhoI site. Four tumours contained p53 gene mutations and three had clonal EBV infection. One case had a bcl-6 rearrangement. In conclusion, our study shows that p16INK4, c-myc and p53 alterations occur in 15%, 25% and 13% of PMBLs, respectively. EBV monoclonality was found in 9% of cases, whereas no abnormality was detected in bcl-1, bcl-2 and N-ras. Thus, none of the common genetic aberrations seen in other types of non-Hodgkin's lymphomas appears to be stringently involved in the pathogenesis of this unique lymphoma type.
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PMID:Molecular features of primary mediastinal B-cell lymphoma: involvement of p16INK4A, p53 and c-myc. 1052 30

The antisense and antigene activity of peptide nucleic acid (PNA) targeted to the human B-cell lymphoma (bcl)-2 gene was evaluated in vitro. Several PNAs complementary to different sequences of bcl-2, including the start codon and the 5'-untranslated region (5'-UTR), were tested. One PNA directed against the AUG start codon and another recognizing the 5'-UTR were able to specifically reduce Bcl-2 protein synthesis in a cell-free system; however, only partial inhibition (80 and 54%, respectively) was obtained when they were used singularly. Complete translation block was obtained with the simultaneous presence of both PNAs. A triplex-forming bis-PNA was targeted to a homopurine sequence on the coding strand of the bcl-2 cDNA. In an in vitro transcription assay this PNA specifically inhibited the transcription of bcl-2 at concentrations as low as 300 nM, with the concomitant appearance of a truncated 200-base-long product. These results demonstrate the ability of PNA to selectively modulate both translation and transcription of bcl-2 in vitro and suggest its potential use as an antisense and an antigene agent in order to downregulate bcl-2 expression in tumors.
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PMID:In vitro transcriptional and translational block of the bcl-2 gene operated by peptide nucleic acid. 1052 98

Thebcl-2oncogene plays an important role in carcinogenesis by inhibiting cell death (apoptosis). It was initially discovered in follicular B cell lymphoma with t(14,18), and subsequently found in other malignant and premalignant lesions. Alteration of the normal controls of cell proliferation is also a significant factor in the multistep process of tumorigenesis. The proliferative activity of a given lesion is commonly valuated by MIB1, a monoclonal antibody to Ki67 proliferation antigen. Immuno-histochemical (IHC) staining expression of bcl-2 and Ki67 was retrospectively investigated in a series of 52 colorectal carcinomas and 56 adenomas according to the avidin-biotin-complex method. The aim of the study was twofold: 1) to investigate any correlation between MIB1 and bcl-2 immunostaining expression in colonic adenomas and carcinomas, 2) to identify any relationship between either marker and several histopathologic parameters including tumor size, pathologic stage, lymph node metastasis, angio-lymphatic invasion, tumor grade and differentiation in colon carcinomas. Bcl-2 was consistently higher in adenomas than in carcinomas. There were 44/56 (78.6%) adenomas, and 27/52 (51.9%) carcinomas positive for bcl-2 (p=0.004). The mean Ki67 labeling index (LI) was 30.05+/-7.6 and 38.12+/-11.01 in adenomas and carcinomas, respectively (p=0.0001). Expression of bcl-2 in carcinoma was significantly associated with a lower mean Ki67 LI and with favorable histopathologic parameters. We conclude that bcl-2 oncoprotein expression is probably an early step in the process of colon carcinogenesis, and its expression may be associated with a favorable clinical course. Furthermore, an inverse relationship exists between bcl-2 and Ki67 in colonic neoplasia. Evaluation of bcl-2 and Ki67 IHC expression in colonic carcinoma should be performed prospectively to determine if their expression is of value in predicting the clinical course in these patients.
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PMID:Correlation of bcl-2 oncoprotein immunohistochemical expression with proliferation index and histopathologic parameters in colorectal neoplasia. 1060 21

Primary brain lymphoma (PBL) is an uncommon extranodal lymphoma. Its incidence is rapidly increasing in both immunocompromised and immunocompetent patients in Western countries. Eighteen cases of PBL were identified during a 16-year period among HIV negative patients in Queen Mary Hospital, Hong Kong. One case of post-transplantation lymphoproliferative disease (PTLD) was positive for Epstein Barr virus (EBV) encoded RNA (EBER) by in situ hybridization. All the remaining 17 immunocompetent cases were classified as diffuse large B-cell lymphoma, except for one case of Burkitt's lymphoma. EBER expression was negative in all 13 cases tested. Immunostaining for bcl-2 and bcl-6 was positive in 8/11 and 6/11 cases tested, with heterogeneous combination of expression and intensity. The incidence rate of PBL in immunocompetent patients was stable at 1.03 per million per year. The incidence of PBL in post transplantation (0.16%) and HIV related setting (0.29%) is also low in Chinese. PBL in Chinese patients is almost uniformly represented by EBV negative, diffuse large B-cell lymphoma, confined to the brain. However, the molecular pathogenesis may be heterogeneous.
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PMID:Incidence and pathology of primary brain lymphoma in Hong Kong Chinese patients. 1072 83

Extranodal marginal zone B-cell lymphoma (MZBL) is a recently recognized low-grade lymphoma that has been well described in other organs such as the stomach and salivary gland. It has only recently been described in skin, where it may be difficult to distinguish from reactive processes and other types of B-cell lymphoma such as follicle center lymphoma. These cases may have been classified as pseudolymphomas in the past. Extranodal MZBL was referred to as mucosa-associated lymphoid tissue (MALT) lymphoma before the Revised European-American Classification of Lymphoid Neoplasms was published in 1994. Important histologic features that aid in the diagnosis of MALT lymphoma are atypical lymphocytes (centrocyte-like and monocytoid B cells) often admixed with plasmacytoid lymphocytes, a prominent plasma cell component, lymphoepithelial lesions, intranuclear inclusions (Dutcher bodies), and reactive germinal centers that may be colonized by neoplastic cells. Immunophenotypic studies demonstrating a B-cell phenotype, light chain restriction, coexpression of CD43, and staining of atypical lymphocytes with bcl-2 support a diagnosis of MALT lymphoma. We studied 11 cases of extranodal MZBL of the skin from the Armed Forces Institute of Pathology files. There were six women and five men ranging in age from 30 to 69 years (median, 54 years). The anatomical sites included the trunk, head and neck areas, and upper extremities. There were no other sites of disease besides the skin in any of the cases. The follow-up period ranged from 5 months to 8 years (median, 24 months). Histologic results included an atypical lymphoid infiltrate with B-cell phenotype, reactive germinal centers, and a variable plasma cell component in all cases. No Dutcher bodies or lymphoepithelial lesions were noted. Extranodal MZBL of skin is a diagnostic challenge because of a heterogeneous cellular infiltrate that may be interpreted as a reactive process. The most significant neoplasm with which it is confused is follicular lymphoma. It is important to recognize the characteristic histologic and immunophenotypic features of extranodal MZBL so that the appropriate therapeutic approach may be applied.
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PMID:Extranodal marginal zone B-cell lymphoma of the skin: a morphologic and immunophenotypic study of 11 cases. 1087 Oct 62

Cancers overexpressing Bcl-2 protein, which prevents programmed cell death (apoptosis), are less sensitive to stresses that produce cellular damage, including chemotherapy. If the level of Bcl-2 protein can be reduced sufficiently using antisense oligonucleotides (ASOs) targeting the gene message, then cytotoxic agents may be rendered more effective in eliminating disease and increasing cure rate. Preclinical studies in SCID mice bearing Bcl-2 overexpressing systemic human B-cell lymphoma (DoHH2) were undertaken to support development of a clinical trial. These data confirm that a combination of an ASO (5 mg/kg) targeting bcl-2 and a low dose of cyclophosphamide (35 mg/kg) was an effective strategy, leading to the eradication of the DoHH2 cells in vivo and cure of the animals. When mice deficient in natural killer cell activity were treated with an ASO, similar results were observed, suggesting that ASO stimulation of the host immune system was not a significant factor in elimination of lymphoma cells. These studies indicate that therapeutic strategies involving the use of an ASO targeting bcl-2 in combination with a cytotoxic agent may improve clinical outcomes.
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PMID:Eradication of human non-Hodgkin's lymphoma in SCID mice by BCL-2 antisense oligonucleotides combined with low-dose cyclophosphamide. 1087 4


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