Expression of the apoptosis-releated genes in patients with newly diagnosed chronic lymphocytic leukemia in clinical data context

Introduction.The given data of fundamental studies of apoptosis processes in B-cell lymphocytic leukemia (B-CLL) testifies about the complexity and variety of mechanisms affecting the kinetics of normal cells and tumor lymphocytes in this disease. It is important to study the severity of clinical manifestations of the disease depending on the expression of the genes that modulate apoptosis.The purposeof the study is to compare the activity of genes encoding apoptosis modulators, the cell cycle and cancer-testicular PRAME protein with clinical manifestations of the disease in primary patients with B-CLL.Materials and methods.The level of expression of the proapoptotic genes FAS, TRAIL, TNFR2, DR4/5 and DR3, as well as the HSP27, XIAP genes, blocking apoptosis was determined in 23 patients with newly diagnosed chronic B-CLL. In addition, expression of genes TP53 and P21 and cancer-testis gene PRAME are tested.Results.According to the multivariate regression analysis, the FAS gene expression in the onset of the disease had the greatest impact on the clinical characteristics of the disease. In this connection, the patients were divided into groups with normal (group) and low gene level (group II). A low level of FAS expression (Me 387 %) was associated with stage II disease (p = 0.03), a large number of lympho cytes (p = 0.001), fewer erythrocytes (p = 0.08), and a lower level of TNFR2 gene expression (p = 0.08), high level of expression of XIAP, HSP27, P21. Overall, the anti-apoptotic potential in Group II patients was higher, which was accompanied by more pronounced clinical manifestations of the disease.Conclusions.The increased anti-apoptotic potential of tumor lymphocytes in newly diagnosed B-CLL is accompanied by a larger tumor mass and greater clinical and hematological manifestation of the disease.

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Distinct gene expression patterns in chronic lymphocytic leukemia defined by usage of specific VH genes

Blood ◽

10.1182/blood-2005-04-1483 ◽

2006 ◽

Vol 107 (5) ◽

pp. 2090-2093 ◽

Cited By ~ 39

Author(s):

Dirk Kienle ◽

Axel Benner ◽

Alexander Kröber ◽

Dirk Winkler ◽

Daniel Mertens ◽

...

Keyword(s):

Gene Expression ◽

Chronic Lymphocytic Leukemia ◽

Expression Patterns ◽

Gene Expression Pattern ◽

Cell Receptor ◽

Lymphocytic Leukemia ◽

Expression Of Genes ◽

Vh Genes ◽

Signaling Activation

The mutation status and usage of specific VH genes such as V3-21 and V1-69 are potentially independent pathogenic and prognostic factors in chronic lymphocytic leukemia (CLL). To investigate the role of antigenic stimulation, we analyzed the expression of genes involved in B-cell receptor (BCR) signaling/activation, cell cycle, and apoptosis control in CLL using these specific VH genes compared to VH mutated (VH-MUT) and VH unmutated (VH-UM) CLL not using these VH genes. V3-21 cases showed characteristic expression differences compared to VH-MUT (up: ZAP70 [or ZAP-70]; down: CCND2, P27) and VH-UM (down: PI3K, CCND2, P27, CDK4, BAX) involving several BCR-related genes. Similarly, there was a marked difference between VH unmutated cases using the V1-69 gene and VH-UM (up: FOS; down: BLNK, SYK, CDK4, TP53). Therefore, usage of specific VH genes appears to have a strong influence on the gene expression pattern pointing to antigen recognition and ongoing BCR stimulation as a pathogenic factor in these CLL subgroups.

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Gene expression profiling for molecular classification of multiple myeloma in newly diagnosed patients

Blood ◽

10.1182/blood-2009-12-261032 ◽

2010 ◽

Vol 116 (14) ◽

pp. 2543-2553 ◽

Cited By ~ 171

Author(s):

Annemiek Broyl ◽

Dirk Hose ◽

Henk Lokhorst ◽

Yvonne de Knegt ◽

Justine Peeters ◽

...

Keyword(s):

Gene Expression ◽

Multiple Myeloma ◽

Gene Expression Profiling ◽

Expression Profiling ◽

Plasma Cells ◽

Medical Science ◽

Protein Tyrosine Phosphatases ◽

Molecular Classification ◽

Newly Diagnosed ◽

Expression Of Genes

Abstract To identify molecularly defined subgroups in multiple myeloma, gene expression profiling was performed on purified CD138+ plasma cells of 320 newly diagnosed myeloma patients included in the Dutch-Belgian/German HOVON-65/GMMG-HD4 trial. Hierarchical clustering identified 10 subgroups; 6 corresponded to clusters described in the University of Arkansas for Medical Science (UAMS) classification, CD-1 (n = 13, 4.1%), CD-2 (n = 34, 1.6%), MF (n = 32, 1.0%), MS (n = 33, 1.3%), proliferation-associated genes (n = 15, 4.7%), and hyperdiploid (n = 77, 24.1%). Moreover, the UAMS low percentage of bone disease cluster was identified as a subcluster of the MF cluster (n = 15, 4.7%). One subgroup (n = 39, 12.2%) showed a myeloid signature. Three novel subgroups were defined, including a subgroup of 37 patients (11.6%) characterized by high expression of genes involved in the nuclear factor kappa light-chain-enhancer of activated B cells pathway, which include TNFAIP3 and CD40. Another subgroup of 22 patients (6.9%) was characterized by distinct overexpression of cancer testis antigens without overexpression of proliferation genes. The third novel cluster of 9 patients (2.8%) showed up-regulation of protein tyrosine phosphatases PRL-3 and PTPRZ1 as well as SOCS3. To conclude, in addition to 7 clusters described in the UAMS classification, we identified 3 novel subsets of multiple myeloma that may represent unique diagnostic entities.

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Efflux-Related Resistance to Norfloxacin, Dyes, and Biocides in Bloodstream Isolates of Staphylococcus aureus

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00430-07 ◽

2007 ◽

Vol 51 (9) ◽

pp. 3235-3239 ◽

Cited By ~ 122

Author(s):

Carmen E. DeMarco ◽

Laurel A. Cushing ◽

Emmanuel Frempong-Manso ◽

Susan M. Seo ◽

Tinevimbo A. A. Jaravaza ◽

...

Keyword(s):

Gene Expression ◽

Staphylococcus Aureus ◽

Efflux Pump ◽

Resistance Mechanism ◽

Efflux Pump Inhibitor ◽

Qrt Pcr ◽

Reverse Transcription Pcr ◽

Environmental Surfaces ◽

Genes Encoding ◽

High Level

ABSTRACT Efflux is an important resistance mechanism in Staphylococcus aureus, but its frequency in patients with bacteremia is unknown. Nonreplicate bloodstream isolates were collected over an 8-month period, and MICs of four common efflux pump substrates, with and without the broad-spectrum efflux pump inhibitor reserpine, were determined (n = 232). A reserpine-associated fourfold decrease in MIC was considered indicative of efflux. Strains exhibiting efflux of at least two of the four substrates were identified (“effluxing strains” [n = 114]). For these strains, MICs with or without reserpine for an array of typical substrates and the expression of mepA, mdeA, norA, norB, norC, and qacA/B were determined using quantitative real-time reverse transcription-PCR (qRT-PCR). A fourfold or greater increase in gene expression was considered significant. The most commonly effluxed substrates were ethidium bromide and chlorhexidine (100 and 96% of effluxing strains, respectively). qRT-PCR identified strains overexpressing mepA (5 [4.4%]), mdeA (13 [11.4%]), norA (26 [22.8%]), norB (29 [25.4%]), and norC (19 [16.7%]); 23 strains overexpressed two or more genes. Mutations probably associated with increased gene expression included a MepR-inactivating substitution and norA promoter region insertions or deletions. Mutations possibly associated with increased expression of the other analyzed genes were also observed. Effluxing strains comprised 49% of all strains studied (114/232 strains), with nearly half of these overexpressing genes encoding MepA, MdeA, and/or NorABC (54/114 strains). Reduced susceptibility to biocides may contribute to persistence on environmental surfaces, and efflux of drugs such as fluoroquinolones may predispose strains to high-level target-based resistance.

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Abstract 191: Transcriptional Regulation of Renin by Nuclear Receptors Co-regulated With Renin

Hypertension ◽

10.1161/hyp.62.suppl_1.a191 ◽

2013 ◽

Vol 62 (suppl_1) ◽

Author(s):

Ko-Ting Lu ◽

Eric T Weatherford ◽

Pimonrat Ketsawatsomkron ◽

Justin L Grobe ◽

Curt D Sigmund

Keyword(s):

Gene Expression ◽

Nuclear Receptors ◽

Estrogen Receptor Alpha ◽

Hormone Receptors ◽

Cell Types ◽

Negative Control ◽

Sirna Duplex ◽

Expression Of Genes ◽

Renin Gene ◽

Genes Encoding

Expression of the renin gene is required to maintain normal morphological and physiological identity of renal juxtaglomerular (JG) cells, yet the mechanisms regulating renin gene transcription remain elusive. We re-examined data from Brunskill et. al (JASN 22:2213, 2011), investigating genome-wide gene expression in JG and other renal cell types. Based on our previous data implicating nuclear receptors (RAR, RXR, VDR, PPARG, Nr2f2 and Nr2f6) in the regulation of mouse and human renin gene expression, we focused our analysis on the expression of genes encoding the 48 nuclear hormone receptors and their co-regulation with renin. Several nuclear receptors have an expression pattern emulating that of renin, that is, they were similarly enriched in JG cells but not in other cell types. These include Esr1, Nr1h4, Ppara, VDR, Nr1i2, Ppard, Hnf4g, Nr1h3, Thrb, Hnf4a, Esrrg, Nr4a3, Nr3c2, and Ar. We tested the hypothesis that a nuclear receptor that is co-regulated with renin may participate in renin gene regulation. To accomplish this, endogenous renin expression was evaluated in renin-expressing As4.1 cells after siRNA-mediated knock down of selected nuclear receptors. Each experiment included a negative control siRNA duplex (NC) that does not target any known genes. By way of example, siRNA-mediated inhibition of estrogen receptor alpha (Esr1) by 70-80% resulted in a 2-fold decrease in renin mRNA (fold change ± SEM: siEsr1: 0.4±0.2, p<0.001 vs NC). Similar results were obtained with a different siRNA targeting Esr1. Interestingly, loss of Esr1 also caused up-regulation of vitamin D receptor (VDR, 2.8±0.7 fold, p<0.001 vs NC) and Nr2f6 (2.0±0.2 fold, p<0.05 vs NC), both of which are known to be negative regulators of renin. Similarly, both renin (0.1±0.02, p<0.001 vs untreated) and Esr1 (0.3±0.1, p<0.05 vs untreated) mRNA were reduced in the kidney from mice treated with deoxycorticosterone acetate (50mg) and receiving 0.15 M NaCl in drinking water for 21 days (DOCA-salt). These data suggest Esr1 may regulate renin expression. Studies are in progress to assess if Esr1 stimulates renin expression on its own or acts by affecting the level of other nuclear receptors; and to determine if other co-regulated nuclear receptors also regulate expression of the renin gene.

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Up-Regulation Mttp and Apob Gene Expression in Rat Liver is Related to Post-Lipectomy Hypertriglyceridemia

Cellular Physiology and Biochemistry ◽

10.1159/000430149 ◽

2015 ◽

Vol 36 (5) ◽

pp. 1767-1777 ◽

Cited By ~ 4

Author(s):

Agnieszka Dettlaff-Pokora ◽

Tomasz Sledzinski ◽

Julian Swierczynski

Keyword(s):

Gene Expression ◽

Fatty Acid Synthase ◽

Protein A ◽

Surgical Removal ◽

Gene Expressions ◽

Transfer Protein ◽

Expression Of Genes ◽

Spot 14 ◽

Genes Encoding ◽

Experimental Rat Model

Background/Aims: The aim of this study was to explain the molecular basis for elevated concentrations of circulating triglycerides (TAGs) after partial surgical removal of adipose tissue (lipectomy) in rats. Methods: The levels of mRNA and protein: a) involved in synthesis of fatty acids and TAGs; b) participating in TAG-rich lipoproteins assembly and secretion; and c) transcription factors essential for maintaining TAG homeostasis were determined by RT-PCR and Western Blot in the livers of control and lipectomized rats. Results: Partial lipectomy was associated with increase: a) in serum and liver concentration of TAGs, and b) in the liver levels of mRNA of microsomal TAG transfer protein (MTP) and apolipoprotein B-100 (ApoB-100). These changes were tightly associated with up-regulation of Hnf1a and Hnf4a gene expression in the liver. Lipectomy was also reflected by a significant increase in the expression of genes encoding: a) fatty acid synthase (FASN), b) glycerol 3-phosphate acyltransferase 1 (GPAT1), diacylglycerol acyltransferases 1 and 2 (DGAT1 and DGAT2), c) spot 14 protein (S14) and SREBP-1 in the liver. Conclusion: Coordinated up-regulation of Mttp, Apob, Hnf1a, Hnf4a, Fasn, Gpam and Dgat (1 and 2) gene expressions may contribute to the increase in circulating and liver concentrations of TAGs after lipectomy in an experimental rat model.

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Evidence of positive regulation of mycobacteriophage D29 early gene expression obtained from an investigation using a temperature-sensitive mutant of the phage

FEMS Microbiology Letters ◽

10.1093/femsle/fnaa176 ◽

2020 ◽

Vol 367 (21) ◽

Author(s):

Shrestha Ghosh ◽

Rahul Shaw ◽

Apurba Sarkar ◽

Sujoy K Das Gupta

Keyword(s):

Gene Expression ◽

Proteome Analysis ◽

Early Gene ◽

Specific Factor ◽

Temperature Sensitive ◽

Expression Of Genes ◽

Infected Cells ◽

Ts Mutant ◽

The Right ◽

High Level

ABSTRACT Mycobacteriophages are phages that infect and kill Mycobacteria, several of which, Mycobacterium tuberculosis (Mtb), for example, cause the disease tuberculosis. Although genomes of many such phages have been sequenced, we have very little insight into how they express their genes in a controlled manner. To address this issue, we have raised a temperature-sensitive (ts) mutant of phage D29 that can grow at 37°C but not at 42°C and used it to perform differential gene expression and proteome analysis studies. Our analysis results indicate that expression of genes located in the right arm, considered to be early expressed, was lowered as the temperature was shifted from 37°C to 42°C. In contrast, expression of those on the left, the late genes were only marginally affected. Thus, we conclude that transcription of genes from the two arms takes place independently of each other and that a specific factor must be controlling the expression of the right arm genes. We also observe that within the right arm itself; there exists a mechanism to ensure high-level synthesis of Gp48, a thymidylate synthase X. Enhanced presence of this protein in infected cells results in delayed lysis and higher phage yields.

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Phytochrome signal-transduction: characterization of pathways and isolation of mutants

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.1995.0139 ◽

1995 ◽

Vol 350 (1331) ◽

pp. 67-74 ◽

Cited By ~ 13

Keyword(s):

Gene Expression ◽

Signal Transduction ◽

Red Light ◽

Signal Transduction Pathway ◽

Regulatory Elements ◽

Signal Transduction Pathways ◽

Expression Of Genes ◽

Genes Encoding ◽

Regulated Gene Expression ◽

Dependent Pathway

The study of phytochrome signalling has yielded a wealth of data describing both the perception of light by the receptor, and the terminal steps in phytochrome-regulated gene expression by a number of transcription factors. We are now focusing on establishing the intervening steps linking phytochrome photoactivation to gene expression, and the regulation and interactions of these signalling pathways. Recent work has utilized both a pharmacological approach in phototrophic soybean suspension cultures and microinjection techniques in tomato to establish three distinct phytochrome signal-transduction pathways: (i) a calcium-dependent pathway that regulates the expression of genes encoding the chlorophyll a/b binding protein ( CAB ) and other components of photosystem II; (ii) a cGMP-dependent pathway that regulates the expression of the gene encoding chalcone synthase ( CHS ) and the production of anthocyanin pigments; and (iii) a pathway dependent upon both calcium and cGMP that regulates the expression of genes encoding components of photosystem I and is necessary for the production of mature chloroplasts. To study the components and the regulation of phytochrome signal-transduction pathways, mutants with altered photomorphogenic responses have been isolated by a number of laboratories. However, with several possible exceptions, little real progress has been made towards the isolation of mutants in positive regulatory elements of the phytochrome signal-transduction pathway. We have characterized a novel phytochrome A (phyA)-mediated far-red light (FR) response in Arabidopsis seedlings which we are currently using to screen for specific phyA signal-transduction mutants.

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Nrg1 Is a Transcriptional Repressor for Glucose Repression of STA1 Gene Expression inSaccharomyces cerevisiae

Molecular and Cellular Biology ◽

10.1128/mcb.19.3.2044 ◽

1999 ◽

Vol 19 (3) ◽

pp. 2044-2050 ◽

Cited By ~ 73

Author(s):

Seok Hee Park ◽

Sang Seok Koh ◽

Jae Hwan Chun ◽

Hye Jin Hwang ◽

Hyen Sam Kang

Keyword(s):

Gene Expression ◽

Zinc Finger Protein ◽

Glucose Repression ◽

Transcriptional Repressor ◽

Dependent Manner ◽

Expression Of Genes ◽

Dnase I Footprinting ◽

Genes Encoding

ABSTRACT Expression of genes encoding starch-degrading enzymes is regulated by glucose repression in the yeast Saccharomyces cerevisiae. We have identified a transcriptional repressor, Nrg1, in a genetic screen designed to reveal negative factors involved in the expression of STA1, which encodes a glucoamylase. TheNRG1 gene encodes a 25-kDa C2H2zinc finger protein which specifically binds to two regions in the upstream activation sequence of the STA1 gene, as judged by gel retardation and DNase I footprinting analyses. Disruption of theNRG1 gene causes a fivefold increase in the level of theSTA1 transcript in the presence of glucose. The expression of NRG1 itself is inhibited in the absence of glucose. DNA-bound LexA-Nrg1 represses transcription of a target gene 10.7-fold in a glucose-dependent manner, and this repression is abolished in bothssn6 and tup1 mutants. Two-hybrid and glutathione S-transferase pull-down experiments show an interaction of Nrg1 with Ssn6 both in vivo and in vitro. These findings indicate that Nrg1 acts as a DNA-binding repressor and mediates glucose repression of the STA1 gene expression by recruiting the Ssn6-Tup1 complex.

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Drought Stress Enhances Up-Regulation of Anthocyanin Biosynthesis in Grapevine leafroll-associated virus 3-Infected in vitro Grapevine (Vitis vinifera) Leaves

Plant Disease ◽

10.1094/pdis-01-17-0104-re ◽

2017 ◽

Vol 101 (9) ◽

pp. 1606-1615 ◽

Cited By ~ 7

Author(s):

Zhen-Hua Cui ◽

Wen-Lu Bi ◽

Xin-Yi Hao ◽

Peng-Min Li ◽

Ying Duan ◽

...

Keyword(s):

Gene Expression ◽

Drought Stress ◽

Vitis Vinifera ◽

Anthocyanin Biosynthesis ◽

Anthocyanin Accumulation ◽

Expression Levels ◽

Expression Of Genes ◽

Genes Encoding ◽

Regulated Gene Expression

Reddish-purple coloration on the leaf blades and downward rolling of leaf margins are typical symptoms of grapevine leafroll disease (GLD) in red-fruited grapevine cultivars. These typical symptoms are attributed to the expression of genes encoding enzymes for anthocyanins synthesis, and the accumulation of flavonoids in diseased leaves. Drought has been proven to accelerate development of GLD symptoms in virus-infected leaves of grapevine. However, it is not known how drought affects GLD expression nor how anthocyanin biosynthesis in virus-infected leaves is altered. The present study used HPLC to determine the types and levels of anthocyanins, and applied reverse transcription quantitative polymerase chain reaction (RT-qPCR) to analyze the expression of genes encoding enzymes for anthocyanin synthesis. Plantlets of Grapevine leafroll-associated virus 3 (GLRaV-3)-infected Vitis vinifera ‘Cabernet Sauvignon’ were grown in vitro under PEG-induced drought stress. HPLC found no anthocyanin-related peaks in the healthy plantlets with or without PEG-induced stress, while 11 peaks were detected in the infected plantlets with or without PEG-induced drought stress, but the peaks were significantly higher in infected drought-stressed plantlets. Increased accumulation of total anthocyanin compounds was related to the development of GLD symptoms in the infected plantlets under PEG stress. The highest level of up-regulated gene expression was found in GLRaV-3-infected leaves with PEG-induced drought stress. Analyses of variance and correlation of anthocyanin accumulation with related gene expression levels found that GLRaV-3-infection was the key factor in increased anthocyanin accumulation. This accumulation involved the up-regulation of two key genes, MYBA1 and UFGT, and their expression levels were further enhanced by drought stress.

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Using muscle gene expression to estimate triacylglyceride deposition, and relative contributions of fatty acid synthesis and fatty acid import in intramuscular fat in cattle

Animal Production Science ◽

10.1071/an14247 ◽

2014 ◽

Vol 54 (9) ◽

pp. 1436 ◽

Cited By ~ 4

Author(s):

B. P. Dalrymple ◽

B. Guo ◽

G. H. Zhou ◽

W. Zhang

Keyword(s):

Gene Expression ◽

Fatty Acid ◽

De Novo ◽

Acid Synthesis ◽

Intramuscular Fat ◽

Muscle Gene Expression ◽

Expression Of Genes ◽

Genes Encoding ◽

Muscle Gene ◽

The Impact

Intramuscular fat content (IMF%) in cattle influences the value of individual animals, especially for higher marbling markets. IMF is triacylglyceride (TAG) in lipid droplets in the intramuscular adipocytes. However, there are many different pathways from feed intake to the final common process of TAG synthesis and storage as IMF. To evaluate the relative importance of different pathways we compared changes in the expression of genes encoding proteins involved in the TAG and fatty acid (FA) synthesis pathways in the longissimus muscle of Piedmontese × Hereford (P×H) and Wagyu × Hereford (W×H) crosses. Based on these changes we have estimated the relative contributions of FA synthesised de novo in the intramuscular adipocyte and the uptake of circulating FA (both free and from TAG), from the diet or synthesised de novo in other tissues, to TAG deposition as IMF. We have analysed the impact of different developmental times and different diets on these processes. Increased de novo FA synthesis in intramuscular adipocytes appeared to contribute more than increased FA uptake from circulation to the additional TAG deposition in W×H compared with P×H cattle between 12 and 25 months (forage diet). Changing diet from forage to concentrate appeared to increase the importance of FA uptake from circulation relative to de novo FA synthesis for TAG synthesis in intramuscular adipocytes. These results are consistent with the literature based on analysis of lipid composition. Gene expression appears to provide a simple assay for identification of the source of FA for the deposition of IMF.

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