Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interactions between immunocompetent cells require the participation of T cell antigen receptor (TCR) and the integrin lymphocyte function-associated molecule-1 (LFA-1, CD11a/CD18). These interactions are mediated by interlinking cytokines, which are important in determining the type of immune response. In the present study, we have shown that in American cutaneous leishmaniasis (ACL) lesions, most infiltrating T cells expressed the alpha beta TCR including those selectively migrating to the epidermis. In contrast, gamma delta T cells were abundant in localized (LCL) and scarce in muco-cutaneous (MCL) and diffuse (DCL) cutaneous leishmaniasis, suggesting a role in effective granulomas. There were differences in the expression of LFA-1 alpha and beta subunits, with most cells expressing LFA-1 beta. The ratio LFA-1 beta/LFA-1 alpha was higher in LCL (11.8:1) than in MCL (3.3:1) and DCL (2.4:1). Similar results were observed in Leishmania mexicana-infected C57BL/6 mice. DCL lesions showed a higher proportion of LFA-1 alpha+ cells than MCL and LCL lesions. A reverse-transcriptase polymerase chain reaction (RT-PCR) analysis of the cytokine profiles showed that most T cells present in the MCL and DCL lesions secrete a mixture of Type 1 and Type 2 cytokine patterns, but in DCL granulomas predominate the Type 2 cytokines. In LCL the cytokine patterns show a preponderance of INF gamma over IL-4, and low levels of IL-5 and IL-10, suggesting a Type 1 cytokine profile.
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PMID:The cutaneous lesion in American leishmaniasis: leukocyte subsets, cellular interaction and cytokine production. 754 1

The BCL10 gene was identified at the breakpoint region of the t(1;14)(p22;q32) translocation in mucosa-associated lymphoid tissue lymphoma. Initially, mutations in the BCL10 gene were reported to occur at a high frequency in various types of lymphomas and solid tumors. However, subsequent studies showed that the mutations were rarely recognized. To evaluate the frequency and spectrum of its mutations in B-cell non-Hodgkin's lymphoma (B-NHL), we screened 56 cases with B-NHL by mutation analysis of exons 2 and 3 of the gene. In addition to 2 polymorphisms, a frame-shift mutation and a missense mutation were identified in 2 cases (3.6%): 1 with diffuse large B-cell lymphoma and the other with mantle cell lymphoma. Both cases showed mutations within exon 3, resulting in a C-terminal truncation in the former and a C-terminal amino acid substitution in the latter. Reverse transcriptase-polymerase chain reaction analysis of the former case revealed that both the mutated and the wild-type alleles were transcribed with or without a sequence modification. Our results, together with recent reports, indicate that BCL10 gene mutations take place in a small population of B-NHL and are not associated with specific histological subtypes.
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PMID:Low frequency of BCL10 gene mutations in B-cell non-Hodgkin's lymphoma. 1137 35

Mantle cell lymphoma (MCL) is a distinct type of non-Hodgkin's lymphoma (NHL) characterized by the t(11;14)(q13;q32), in which the ccnd1 gene is juxtaposed with the immunoglobulin heavy chain gene, resulting in up-regulation of cyclin D1. Cyclin D1 overexpression is a useful finding that supports the diagnosis of MCL. In this study, we used a 5' --> 3' exonuclease-based real-time reverse-transcriptase polymerase chain reaction (RT-PCR) method to quantify cyclin D1 mRNA in 108 B-cell NHL and nonneoplastic specimens, including 25 cases of MCL. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was also quantified to normalize cyclin D1 mRNA levels, and the data were expressed as a cyclin D1 to GAPDH ratio. At each anatomic site, MCL cases had higher cyclin D1 levels than other types of NHL or nonneoplastic specimens, without overlap. For example, in lymph node specimens, the median cyclin D1/GAPDH ratio was 147 (range, 94-160) in MCL, compared with 8.6 (range, 4-18) in chronic lymphocytic leukemia/small lymphocytic lymphoma; 5.8 (range, 1.8-24) in follicular lymphoma; 4.8 in one case of marginal zone lymphoma; and 20.2 (range, 5.8-44) in reactive specimens. Statistical analysis using one-way analysis of variance (ANOVA) showed that MCL cases had significantly higher cyclin D1 levels than other groups (P <.05). In peripheral blood specimens involved by MCL, cyclin D1 levels correlated with extent of involvement. We conclude that this real-time RT-PCR method to quantify cyclin D1 expression is helpful in distinguishing MCL from other types of B-cell NHL and from nonneoplastic specimens. This method is rapid, can be applied to the analysis of fluid specimens, and obviates the need for time-consuming and laborious detection methods that are required by traditional semi-quantitative RT-PCR methods.
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PMID:Real-time RT-PCR assay for quantifying cyclin D1 mRNA in B-cell non-Hodgkin's lymphomas. 1201 Dec 61

Sequence variants at the TERT-CLPTM1L locus in chromosome 5p have been recently associated with disposition for various cancers. Here we show that this locus including the gene encoding the telomerase reverse-transcriptase TERT at 5p13.33 is rarely but recurrently targeted by somatic chromosomal translocations to IGH and non-IG loci in B-cell neoplasms, including acute lymphoblastic leukemia, chronic lymphocytic leukemia, mantle cell lymphoma and splenic marginal zone lymphoma. In addition, cases with genomic amplification of TERT locus were identified. Tumors bearing chromosomal aberrations involving TERT showed higher TERT transcriptional expression and increased telomerase activity. These data suggest that deregulation of TERT gene by chromosomal abnormalities leading to increased telomerase activity might contribute to B-cell lymphomagenesis.
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PMID:Deregulation of the telomerase reverse transcriptase (TERT) gene by chromosomal translocations in B-cell malignancies. 2046 May 2

Primary mediastinal large B-cell lymphoma (PMBL) is a mature large B-cell lymphoma of putative thymic B-cell origin involving the mediastinum with younger age distribution and better prognosis than diffuse large B-cell lymphoma (DLBCL), not otherwise specified. Recently, based on gene expression profile analysis and morphologic findings, cases of PMBL without mediastinal involvement have been reported. In this study, we analyzed 3 cases of nodal DLBCL with morphologic features of PMBL presenting in submandibular or supraclavicular lymph nodes, in middle-aged to elderly patients, 2 of them without clinical or radiologic evidence of mediastinal involvement. The 3 patients presented with stage I/II disease and had excellent response to R-CHOP/R-EPOCH therapy. The 3 cases showed MAL expression and were positive for CD23 and/or CD30. All 3 cases expressed cyclin D1 with copy number gains of CCND1 gene but without rearrangement. There was no rearrangement of CIITA or PDL1/PDL2. Reverse transcriptase-multiplex ligation-dependent probe amplification, a mRNA-based gene expression profile analysis revealed high probability of PMBL (87.6%, 98.7%, and 99%) in these 3 cases. Targeted next-generation sequencing analysis showed SOCS1 mutations in the 3 cases, and TNFAIP3 and XPO1 mutations in one, further supporting the diagnosis of PMBL. In conclusion, we report 3 cases of nodal PMBL, 2 of them without mediastinal mass, and expression of cyclin D1 due to copy number gains of CCND1 gene, a diagnostic pitfall with mantle cell lymphoma and DLBCL, not otherwise specified.
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PMID:Cyclin D1-positive Mediastinal Large B-Cell Lymphoma With Copy Number Gains of CCND1 Gene: A Study of 3 Cases With Nonmediastinal Disease. 3021 26