scholarly journals Kaposi's sarcoma-associated herpesvirus-infected primary effusion lymphoma has a plasma cell gene expression profile

2003 ◽  
Vol 100 (18) ◽  
pp. 10399-10404 ◽  
Author(s):  
R. G. Jenner ◽  
K. Maillard ◽  
N. Cattini ◽  
R. A. Weiss ◽  
C. Boshoff ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profile ◽  
Plasma Cell ◽  
Expression Profile ◽  
Kaposi's Sarcoma ◽  
Primary Effusion Lymphoma ◽  
Kaposi’S Sarcoma ◽  
Cell Gene Expression ◽  
Kaposi’S Sarcoma Associated Herpesvirus ◽  
Cell Gene

The t(14;18) defines a unique subset of diffuse large B-cell lymphoma with a germinal center B-cell gene expression profile

Blood ◽  
2002 ◽  
Vol 99 (7) ◽  
pp. 2285-2290 ◽  
Author(s):  
James Z. Huang ◽  
Warren G. Sanger ◽  
Timothy C. Greiner ◽  
Louis M. Staudt ◽  
Dennis D. Weisenburger ◽  
...  
Keyword(s):  
Gene Expression ◽  
B Cell ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Germinal Center ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Germinal Center B Cell ◽  
Cell Gene Expression ◽  
Cell Gene

Recently we have identified subgroups of de novo primary diffuse large B-cell lymphoma (DLBCL) based on complementary DNA microarray-generated gene expression profiles. To correlate the gene expression profiles with cytogenetic abnormalities in these DLBCLs, we examined the occurrence of the t(14;18)(q32;q21) in the 2 distinctive subgroups of DLBCL: one with the germinal center B-cell gene expression signature and the other with the activated B cell–like gene expression signature. The t(14;18) was detected in 7 of 35 cases (20%). All 7 t(14;18)-positive cases had a germinal center B-cell gene expression profile, representing 35% of the cases in this subgroup, and 6 of these 7 cases had very similar gene expression profiles. The expression of bcl-2 and bcl-6 proteins was not significantly different between the t(14;18)-positive and -negative cases, whereas CD10 was detected only in the group with the germinal center B-cell expression profile, and CD10 was most frequently expressed in the t(14;18)-positive cases. This study supports the validity of subdividing DLBCL into 2 major subgroups by gene expression profiling, with the t(14;18) being an important event in the pathogenesis of a subset of DLBCL arising from germinal center B cells. CD10 protein expression is useful in identifying cases of DLBCL with a germinal center B-cell gene expression profile and is often expressed in cases with the t(14;18).

scholarly journals Kaposi's Sarcoma-Associated Herpesvirus Latent and Lytic Gene Expression as Revealed by DNA Arrays

2001 ◽  
Vol 75 (2) ◽  
pp. 891-902 ◽  
Author(s):  
Richard G. Jenner ◽  
M. Mar Albà ◽  
Chris Boshoff ◽  
Paul Kellam
Keyword(s):  
Gene Expression ◽  
Kaposi's Sarcoma ◽  
Primary Effusion Lymphoma ◽  
Human Herpesvirus ◽  
Kaposi’S Sarcoma ◽  
Lytic Replication ◽  
Dna Arrays ◽  
Nylon Membrane ◽  
Kaposi's Sarcoma Associated Herpesvirus ◽  
Kaposi’S Sarcoma Associated Herpesvirus

ABSTRACT Kaposi's sarcoma-associated herpesvirus (KSHV; human herpesvirus 8) is associated with three human tumors, Kaposi's sarcoma, primary effusion lymphoma (PEL), and multicentric Castleman's disease. KSHV encodes a number of homologs of cellular proteins involved in the cell cycle, signal transduction, and modulation of the host immune response. Of the virus complement of over 85 open reading frames (ORFs), the expression of only a minority has been characterized individually. We have constructed a nylon membrane-based DNA array which allows the expression of almost every ORF of KSHV to be measured simultaneously. A PEL-derived cell line, BC-3, was used to study the expression of KSHV during latency and after the induction of lytic replication. Cluster analysis, which arranges genes according to their expression profile, revealed a correlation between expression and assigned gene function that is consistent with the known stages of the herpesvirus life cycle. Furthermore, latent and lytic genes thought to be functionally related cluster into groups. The correlation between gene expression and function also infers possible roles for KSHV genes yet to be characterized.

scholarly journals DNA Binding and Modulation of Gene Expression by the Latency-Associated Nuclear Antigen of Kaposi's Sarcoma-Associated Herpesvirus

2001 ◽  
Vol 75 (17) ◽  
pp. 7882-7892 ◽  
Author(s):  
Alexander C. Garber ◽  
Marla A. Shu ◽  
Jianhong Hu ◽  
Rolf Renne
Keyword(s):  
Gene Expression ◽  
Dna Binding ◽  
Kaposi's Sarcoma ◽  
Primary Effusion Lymphoma ◽  
Kaposi’S Sarcoma ◽  
Nuclear Antigen ◽  
Viral Gene ◽  
Mobility Shift ◽  
Kaposi's Sarcoma Associated Herpesvirus ◽  
Kaposi’S Sarcoma Associated Herpesvirus

ABSTRACT Kaposi's sarcoma-associated herpesvirus (KSHV) is associated with Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. The latency-associated nuclear antigen (LANA) is highly expressed in these malignancies and has been shown to play an important role in episomal maintenance, presumably by binding to a putative oriP. In addition, LANA modulates cellular and viral gene expression and interacts with the cellular tumor suppressors p53 and retinoblastoma suppressor protein. Many of these features are reminiscent of Epstein-Barr virus nuclear antigens (EBNAs), a family of six proteins expressed during latency. EBNA-1 is required for episome maintenance, binds to oriP, and strongly activates transcription from two promoters, including its own. We have previously shown that LANA can transactivate its own promoter and therefore asked whether LANA, like EBNA-1, activates transcription by direct binding to DNA. By using recombinant LANA expressed from vaccinia virus vectors for electrophoretic mobility shift assays, we found that LANA does not bind to its own promoter. In contrast, LANA binds specifically to sequences containing an imperfect 20-bp palindrome in the terminal repeat (TR) of KSHV. We further show that the C-terminal domain of LANA is sufficient for site-specific DNA binding. Unlike EBNA-1, which activates transcription through binding of oriP, we found that LANA inhibits transcription from a single TR binding site. A multimerized TR as found in the viral genome results in strong transcriptional suppression when linked to a heterologous promoter. These data suggest that LANA, although fulfilling functions similar to those of EBNA-1, does so by very different mechanisms.

scholarly journals A Single-Cell Gene-Expression Profile Reveals Inter-Cellular Heterogeneity within Human Monocyte Subsets

PLoS ONE ◽  
2015 ◽  
Vol 10 (12) ◽  
pp. e0144351 ◽  
Author(s):  
Susanne T. Gren ◽  
Thomas B. Rasmussen ◽  
Sabina Janciauskiene ◽  
Katarina Håkansson ◽  
Jens G. Gerwien ◽  
...  
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Human Monocyte ◽  
Cellular Heterogeneity ◽  
Monocyte Subsets ◽  
Cell Gene Expression ◽  
Cell Gene

scholarly journals Gene expression profile of AIDS-related Kaposi's sarcoma

BMC Cancer ◽  
2003 ◽  
Vol 3 (1) ◽  
Author(s):  
Marion Cornelissen ◽  
Antoinette C van der Kuyl ◽  
Remco van den Burg ◽  
Fokla Zorgdrager ◽  
Carel JM van Noesel ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Kaposi's Sarcoma ◽  
Kaposi’S Sarcoma

scholarly journals Kaposi’s Sarcoma-Associated Herpesvirus Drives a Super-Enhancer-Mediated Survival Gene Expression Program in Primary Effusion Lymphoma

mBio ◽  
2020 ◽  
Vol 11 (4) ◽  
Author(s):  
Mark Manzano ◽  
Thomas Günther ◽  
Hyunwoo Ju ◽  
John Nicholas ◽  
Elizabeth T. Bartom ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Kaposi's Sarcoma ◽  
Primary Effusion Lymphoma ◽  
Kaposi’S Sarcoma ◽  
Cellular Transcription Factor ◽  
Super Enhancer ◽  
Kaposi's Sarcoma Associated Herpesvirus ◽  
Kaposi’S Sarcoma Associated Herpesvirus ◽  
Expression Program

ABSTRACT Kaposi’s sarcoma-associated herpesvirus (KSHV) causes primary effusion lymphoma (PEL). The cellular transcription factor (TF) interferon (IFN) regulatory factor 4 (IRF4) is an essential oncogene in PEL, but its specific role in PEL and how KSHV deregulates IRF4 remain unknown. Here, we report that the KSHV latency protein viral interferon regulatory factor 3 (vIRF3) cooperates with IRF4 and cellular BATF (basic leucine zipper ATF-like TF) to drive a super-enhancer (SE)-mediated oncogenic transcriptional program in PEL. Chromatin immunoprecipitation coupled with next-generation sequencing (ChIP-Seq) experiments demonstrated that IRF4, vIRF3, and BATF cooccupy the SEs of key survival genes, in a pattern that is distinct from those seen with other IRF4-driven malignancies. All three proteins cooperatively drive SE-mediated IRF4 overexpression. Inactivation of vIRF3 and, to a lesser extent, BATF phenocopies the gene expression changes and loss of cellular viability observed upon inactivation of IRF4. In sum, this work suggests that KSHV vIRF3 and cellular IRF4 and BATF cooperate as oncogenic transcription factors on SEs to promote cellular survival and proliferation in KSHV-associated lymphomas. IMPORTANCE Kaposi’s sarcoma-associated herpesvirus (KSHV) causes the aggressive disease primary effusion lymphoma (PEL). Here, we show that a viral transcription factor (vIRF3) cooperates with the cellular transcription factor IRF4 to control an oncogenic gene expression program in PEL cells. These proteins promote KSHV-mediated B cell transformation by activating the expression of prosurvival genes through super-enhancers. Our report thus demonstrates that this DNA tumor virus encodes a transcription factor that functions with cellular IRF4 to drive oncogenic transcriptional reprogramming.

scholarly journals Generating AML-Specific Peripheral Blood Autologous Cytotoxic T-Lymphocytes (CTLs)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5806-5806
Author(s):  
Rohtesh S. Mehta ◽  
Xiaohua Chen ◽  
Antony Jeyaraj ◽  
Paul Szabolcs
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
T Cell ◽  
Gene Expression Profile ◽  
Cell Lines ◽  
Expression Profile ◽  
Leukemia Cell ◽  
P Value ◽  
Cell Gene Expression ◽  
Cell Gene

Abstract Background: Ex-vivo expansion of CBT-cells using CD3/CD28 co-stimulatory beads, IL-2 + IL-7 and subsequent priming against leukemia cell lines using IL-15 generated specific CTLs. [1, 2] Hypothesis: We hypothesized that (a) patient-derived AML-specific PB auto CTLs could be generated with immune-stimulatory culture condition (b) Resistant AML samples would possess gene expression profiles similar to MDSCs (myeloid-derived suppressor cells) (c) Frequency of Tregs (CD4+CD25brightFoxP3+) and T-cell co-signaling molecules gene expression will be different between effective and ineffective CTLs. Methods: AML & auto T-cells were purified from cryopreserved PBMC of AML patients admitted with acute blast crisis (n=8). AML blasts were sustained in StemSpan™ Serum-Free media [STEMCELL Technologies] with MSC support + cytokine cocktail (IL-3, SCF, FLT3L, GMCSF, IL-4). T-cells were expanded in culture for 2 weeks as reported [1, 2] and subsequently primed with γ-irradiated auto AML weekly X 3 with IL15 + CD28ab [BD Biosciences]. At the end of week 3 (EOW3), cytotoxicity was assessed against AML and irrelevant targets - IM9 (lymphoid) and U937 (myeloid) cell lines, loaded with BATDA at an E:T ratio of 40:1, 20:1, 10:1 and 5:1 using DELFIA® EuTDA assay.[2] IFN-γ ELISPOT assay against same targets was also done.[2] RT-qPCR analysis was performed on AML & T-cells before and after priming, using Power SYBR® Green master mix (Thermo Fisher Scientific) and StepOne Plus system [Life Technologies]. Two-tailed student t-testcompared experimental groups. Results · T-cells expanded in all samples (n=8) with a median expansion of 155-fold (range 11-489), at EOW3. · ELISPOT assay was positive in 4/8 samples. [Fig 1] · CTL assay was difficult to standardize for primary AML blasts due to high degree of spontaneous apoptosis (>30% spontaneous release [SR]). · 2/8 samples were deemed evaluable (SR<30%). · Both samples showed AML-specific lysis. [Fig 2] · Overall, AML-specific autologous CTL could be generated from 5 of 8 samples based on ELISPOT & CTL assays, regardless of original FAB immunophenotype, not shown. · Tregs proportion declined significantly in effective CTLs post-priming as compared to pre-priming (56% to 24%, p-value 0.046, n=4). [Fig 3] · T-cell gene expression profiling showed significant differences in effective vs ineffective CTLs. [Table 1] · Resistant AML (n=3) had up-regulated downstream markers associated with MDSC generation compared to “non-resistant” AML (n=5). [Table 2] Conclusions (a) AML-specific auto CTLs can be generated (b) Tregs decreased with priming in effective CTLs (c) differential T-cell gene expression profile exists between effective and ineffective CTLs (d) AML gene expression suggests MDSC-like profile in resistant samples.Abstract 5806. TABLE 1:T-CELL GENE EXPRESSION PROFILE (POST VS PRE-PRIMING)Effective CTLs (n=5)Ineffective CTLs (n=3)GeneΔΔ Ct(Post - Pre) (mean, SEM)P-valueFold change (mean, SEM)ΔΔ Ct(Post - Pre) (mean, SEM)P-valueFold change (mean, SEM)4-1BB-3.17 (0.76)0.02514 (7.7)1.98 (1.04)0.190.39 (0.22)HVEM-2.43 (0.61)0.0287.3 (3.7)0.14 (1.65)0.951.57 (1.28)LIGHT-3.62 (0.73)0.01617.3 (7.3)1.78 (1.84)0.441.1 (0.98)PRKC-α-2.03 (0.47)0.0234.6 (1.1)1.89 (0.36)0.0340.29 (0.08)PRKC-θ-3.36 (0.59)0.0113.7 (6.7)0.25 (0.59)0.710.99 (0.41)LAIR1-3.81 (0.42)0.00316.2 (5.6)-1.35 (2.20)0.6017.15 (16.5)PP2A-2.40 (0.57)0.0256.7 (2.6)0.49 (1.57)0.791.89 (1.52)2B4-1.53 (1.14)0.274.98 (1.82)-3.48 (0.11)0.0211.2 (0.9)LTA-α-1.18 (0.78)0.233.61 (2.11)2.69 (0.18)0.0430.16 (0.02)LTA-β-0.93 (0.63)0.242.49 (0.99)2.24 (0.47)0.0420.23 (0.08) TABLE 2: GENE EXPRESSION PROFILE RESISTANT VS NON-RESISTANT AML Gene ΔΔ Ct (mean, SEM) 95% CI P-value Relative fold change JAK1 -4.63 (1.98) -9.48 0.21 0.0579 24.83 JAK2 -5.38 (0.94) -7.67 -3.08 0.0012 41.52 JAK3 -5.90 (2.17) -12.81 1.01 0.0726 59.77 S100A8 -7.16 (2.66) -14.01 -0.32 0.0432 143.27 S100A9 -8.31 (2.75) -15.04 -1.59 0.0233 318.37 c-myc -2.78 (0.59) -4.24 -1.33 0.0034 6.89 Refs: 1.Davis et al. Cancer Research 2010;70(13):5249 2.Jeyaraj A, Chen X, Szabolcs P. IL-15 Induced Polyclonal CTL Generated From Expanded CBT Cells Against Leukemia Cell Lines Constitutes IFN-γ Producing Cells and TCRγδ Cells. ASH 2012 Annual Meeting Figure 1 Figure 1. Figure 2 Figure 2. Figure 3 Figure 3. Disclosures No relevant conflicts of interest to declare.

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