PU.1 protein expression has a positive linear association with protein expression of germinal centre B cell genes includingBCL-6, CD10, CD20 andCD22: identification of PU.1 putative binding sites in theBCL-6 promotor

2005 ◽  
Vol 206 (3) ◽  
pp. 312-319 ◽  
Author(s):  
Emina Torlakovic ◽  
Agnieszka Malecka ◽  
June H Myklebust ◽  
Anne Tierens ◽  
Hans-Christian Aasheim ◽  
...  
Keyword(s):  
Protein Expression ◽  
B Cell ◽  
Binding Sites ◽  
Germinal Centre ◽  
Linear Association

BCL2 gene aberration as an IPI-independent marker for poor outcome in non-germinal-centre diffuse large B cell lymphoma

2009 ◽  
Vol 62 (10) ◽  
pp. 903-907 ◽  
Author(s):  
E C Obermann ◽  
M Csato ◽  
S Dirnhofer ◽  
A Tzankov
Keyword(s):  
Protein Expression ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Germinal Centre ◽  
Individual Risk ◽  
Large B Cell Lymphoma ◽  
Bcl2 Protein ◽  
Worse Prognosis ◽  
Large B Cell

Aim:Diffuse large B cell lymphoma (DLBCL) is the most common lymphoid malignancy in the western hemisphere, and is characterised by a highly variable outcome that impedes individual risk assessment. Lacking reliable biomarkers, the international prognostic index (IPI) has been the most reliable factor to predict survival and stratify patients for therapy. The aim of this study was to investigate the frequency and potential prognostic role of BCL2 aberrations on the chromosomal level and the protein level in a large DLBCL collective.Methods:Fluorescence in situ hybridisation (FISH) with commercially available dual-colour break-apart probes and immunohistochemistry were used to assess BCL2 gene abnormalities and bcl2 protein expression on validated tissue microarrays containing 224 well-characterised cases of primary DLBCL.Results:FISH analysis of BCL2 revealed a break in 40/215 cases (19%) and a gain in 66/171 (39%) cases. Only BCL2 gains correlated with bcl2 protein expression (p = 0.001). Presence of any BCL2 gene abnormality, particularly gains, correlated independently of the IPI with a significantly worse prognosis in DLBCL of non-germinal centre (non-GC) phenotype as opposed to DLBCL of non-GC type without this genetic alteration (p = 0.003). DLBCL of germinal centre phenotype did not show this association.Conclusions:Cases of DLBCL of the non-GC type with BCL2 gene aberration are accompanied by a significantly worse prognosis as opposed to cases without such gene abnormalities. It may be helpful to asses BCL2 gene abnormalities by FISH in addition to assessing established parameters for individual risk estimation in DLBCL.

Transcriptional regulation of human organic anion transporter 1 by B-cell CLL/lymphoma 6

2014 ◽  
Vol 307 (11) ◽  
pp. F1283-F1291 ◽  
Author(s):  
Waja Wegner ◽  
Gerhard Burckhardt ◽  
Maja Henjakovic
Keyword(s):  
Protein Expression ◽  
B Cell ◽  
Binding Sites ◽  
Organic Anion ◽  
Organic Anion Transporter ◽  
Site Directed Mutagenesis ◽  
Expression Vectors ◽  
Mobility Shift ◽  
Opossum Kidney ◽  
Anion Transporter

The human organic anion transporter 1 (OAT1) is crucial for the excretion of organic anions in renal proximal tubular cells and has been classified as a clinically relevant transporter in the kidneys. Our previous study indicated that renal male-predominant expression of rat Oat1 and Oat3 appears to be regulated by transcription factor B-cell CLL/lymphoma 6 (BCL6). The aim of this study was to characterize the effect of BCL6 on human OAT1 promoter and on the transcription of OAT1 mediated by hepatocyte nuclear factor-1α (HNF-1α). Luciferase assays were carried out in opossum kidney (OK) cells transiently transfected with promoter constructs of OAT1, expression vectors for BCL6 and HNF-1α, and the empty control vectors. BCL6 and HNF-1α binding on OAT1 promoter was analyzed using electrophoretic mobility shift assay (EMSA). Protein expression of HNF-1α was investigated by Western blot analysis. Site-directed mutagenesis was used to introduce mutations into BCL6 and HNF-1α binding sites within the OAT1 promoter. BCL6 enhanced the promoter activity of OAT1 independently of predicted BCL6 binding sites but was dependent on HNF-1α response element and HNF-1α protein. Coexpression of BCL6 and HNF-1α induced an additive effect on OAT1 promoter activation compared with BCL6 or HNF-1α alone. BCL6 does not bind directly or indirectly to OAT1 promoter but increases the protein expression of HNF-1α and thereby indirectly enhances OAT1 gene transcription. BCL6 constitutes a promising candidate gene for the regulation of human OAT1 transcription and other renal and/or hepatic drug transporters that have been already shown to be activated by HNF-1α.

Receptor Mediated Binding of the Fibrinolytic Components, Plasminogen and Urokinase, to Peripheral Blood Cells

1987 ◽  
Vol 58 (03) ◽  
pp. 936-942 ◽  
Author(s):  
Lindsey A Miles ◽  
Edward F Plow
Keyword(s):  
T Cells ◽  
B Cell ◽  
Peripheral Blood ◽  
Binding Sites ◽  
Blood Cells ◽  
High Capacity ◽  
Red Cells ◽  
Peripheral Blood Cells ◽  
Cellular Functions ◽  
Fibrinolytic Proteins

SummaryGlu-plasminogen binds to platelets; the monocytoid line, U937, and the human fetal fibroblast line, GM1380 bind both plasminogen and its activator, urokinase. This study assesses the interaction of these fibrinolytic proteins with circulating human blood cells. Plasminogen bound minimally to red cells but bound saturably and reversibly to monocytes, granulocytes and lymphocytes with apparent Kd values of 0.9-1.4 μM. The interactions were of high capacity with 1.6 to 49 × 105 sites/cell and involved the lysine binding sites of plasminogen. Both T cells and non-rosetting lymphocytes and two B cell lines saturably bound plasminogen. Urokinase bound saturably to gianulocytes, monocytes, non-rosetting lymphocytes and a B cell line, but minimally to T cells, platelets and red cells. Therefore, plasminogen binding sites of high capacity, of similar affinities, and with common recognition specificities are expressed by many peripheral blood cells. Urokinase receptors are also widely distributed, but less so than plasminogen binding sites. The binding ol plasminogen and/ or urokinase to these cells may lead to generation of cell- associated proteolytic activity which contributes to a variety of cellular functions.

scholarly journals Prognostic significance of bcl-2 protein expression in aggressive non- Hodgkin's lymphoma. Groupe d'Etude des Lymphomes de l'Adulte (GELA)

Blood ◽  
1996 ◽  
Vol 87 (1) ◽  
pp. 265-272 ◽  
Author(s):  
O Hermine ◽  
C Haioun ◽  
E Lepage ◽  
MF d'Agay ◽  
J Briere ◽  
...  
Keyword(s):  
Overall Survival ◽  
Protein Expression ◽  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Prognostic Significance ◽  
Hodgkin's Lymphoma ◽  
Independent Effect ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Large B Cell

Abstract Little is known about the expression of bcl-2 protein in intermediate and high grade non-Hodgkin's lymphoma (NHL) and its clinical and prognostic significance. We performed immunohistochemical analysis of bcl-2 expression in tumoral tissue sections of 348 patients with high or intermediate grade NHL. These patients were uniformly treated with adriamycin, cyclophosphamide, vindesine, bleomycin, and prednisone (ACVBP) in the induction phase of the LNH87 protocol. Fifty eight cases were excluded due to inadequate staining. Of the 290 remaining patients, 131 (45%) disclosed homogeneous positivity (high bcl-2 expression) in virtually all tumor cells, whereas 65 (23%) were negative and 94 (32%) exhibited intermediate staining. High bcl-2 expression was more frequent in B-cell NHL (109 of 214, 51%) than in T- cell NHL (6 of 35, 17%) (P = .0004), and was heterogeneously distributed among the different histological subtypes. Further analysis was performed on the 151 patients with diffuse large B-cell lymphoma (centroblastic and immunoblastic) to assess the clinical significance and potential prognostic value of bcl-2 expression in the most frequent and homogeneous immunohistological subgroup. High bcl-2 expression, found in 44% of these patients (67 of 151), was more frequently associated with III-IV stage disease (P = .002). Reduced disease-free survival (DFS) (P < .01) and overall survival (P < .05) were demonstrated in the patients with high bcl-2 expression. Indeed, the 3-year estimates of DFS and overall survival were 60% and 61%, respectively (high bcl-2 expression) versus 82% and 78%, respectively (negative/intermediate bcl-2 expression). A multivariate regression analysis confirmed the independent effect of bcl-2 protein expression on DFS. Thus bcl-2 protein expression, as demonstrated in routinely paraffin-embedded tissue, appears to be predictive of poor DFS, in agreement with the role of bcl-2 in chemotherapy-induced apoptosis. It might be considered as a new independent biologic prognostic parameter, which, especially in diffuse large B-cell NHL, could aid in the identification of patient risk groups.

BCL2 protein expression parallels its mRNA level in normal and malignant B cells

Blood ◽  
2004 ◽  
Vol 104 (9) ◽  
pp. 2936-2939 ◽  
Author(s):  
Yulei Shen ◽  
Javeed Iqbal ◽  
James Z. Huang ◽  
Guimei Zhou ◽  
Wing C. Chan
Keyword(s):  
B Cells ◽  
Protein Expression ◽  
B Cell ◽  
Posttranscriptional Regulation ◽  
Cell Lymphoma ◽  
Dominant Role ◽  
Mrna Level ◽  
B Cell Lymphoma ◽  
Transcriptional Level ◽  
Bcl2 Protein

Abstract The regulation of B-cell lymphoma 2 (BCL2) protein expression in germinal center (GC) B cells has been controversial. Previous reports have indicated posttranscriptional regulation plays a dominant role. However, a number of recent studies contradicted these reports. Using real-time polymerase chain reaction (PCR) and Standardized Reverse Transcriptase-PCR (StaRT-PCR), we measured the level of mRNA expression in GC, mantle zone (MNZ), and marginal zone (MGZ) cells from laser capture microdissection. Both quantitative RT-PCR measurements of microdissected GC cells from tonsils showed that GC cells had low expression of BCL2 transcripts commensurate with the low protein expression level. These results are in agreement with microarray studies on fluorescence-activated cell sorter (FACS)-sorted cells and microdissected GC cells. We also examined BCL2 mRNA and protein expression on a series of 30 cases of diffuse large B-cell lymphoma (DLBCL) and found, in general, a good correlation. The results suggested that BCL2 protein expression is regulated at the transcriptional level in normal B cells and in the neoplastic cells in most B-cell lymphoproliferative disorders.

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