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https://www.readbyqxmd.com/read/27681508/alternative-splice-variants-modulates-dominant-negative-function-of-helios-in-t-cell-leukemia
#1
Shaorong Zhao, Wei Liu, Yinghui Li, Pengjiang Liu, Shufang Li, Daolei Dou, Yue Wang, Rongcun Yang, Rong Xiang, Feifei Liu
The molecular defects which lead to multistep incidences of human T-cell leukemia have yet to be identified. The DNA-binding protein Helios (known as IKZF2), a member of the Ikaros family of Krüppel-like zinc-finger proteins, functions pivotally in T-cell differentiation and activation. In this study, we identify three novel short Helios splice variants which are T-cell leukemic specific, and demonstrate their dominant-negative function. We then test the cellular localization of distinct Helios isoforms, as well as their capability to form heterodimer with Ikaros, and the association with complexes comprising histone deacetylase (HDAC)...
2016: PloS One
https://www.readbyqxmd.com/read/27635087/atherosclerosis-driven-treg-plasticity-results-in-formation-of-a-dysfunctional-subset-of-plastic-ifn%C3%AE-th1-tregs
#2
Matthew J Butcher, Adam R Filipowicz, Tayab C Waseem, Christopher McGary, Kevin J Crow, Nathaniel Magilnick, Mark Boldin, Patric S Lundberg, Elena Galkina
RATIONALE: Foxp3(+)T regulatory cells (Tregs) are key players in maintaining immune homeostasis. Evidence suggests that Tregs respond to environmental cues to permit or suppress inflammation. In atherosclerosis, Th1-driven inflammation affects Treg homeostasis, but the mechanisms governing this phenomenon are unclear. OBJECTIVE: Here, we address whether atherosclerosis impacts Treg plasticity and functionality in Apoe(-/-) mice, and what effect Treg plasticity might have on the pathology of atherosclerosis...
September 15, 2016: Circulation Research
https://www.readbyqxmd.com/read/27297792/integrated-mate-pair-and-rna-sequencing-identifies-novel-targetable-gene-fusions-in-peripheral-t-cell-lymphoma
#3
Rebecca L Boddicker, Gina L Razidlo, Surendra Dasari, Yu Zeng, Guangzhen Hu, Ryan A Knudson, Patricia T Greipp, Jaime I Davila, Sarah H Johnson, Julie C Porcher, James B Smadbeck, Bruce W Eckloff, Daniel D Billadeau, Paul J Kurtin, Mark A McNiven, Brian K Link, Stephen M Ansell, James R Cerhan, Yan W Asmann, George Vasmatzis, Andrew L Feldman
Peripheral T-cell lymphomas (PTCLs) represent a heterogeneous group of T-cell malignancies that generally demonstrate aggressive clinical behavior, often are refractory to standard therapy, and remain significantly understudied. The most common World Health Organization subtype is PTCL, not otherwise specified (NOS), essentially a "wastebasket" category because of inadequate understanding to assign cases to a more specific diagnostic entity. Identification of novel fusion genes has contributed significantly to improving the classification, biologic understanding, and therapeutic targeting of PTCLs...
September 1, 2016: Blood
https://www.readbyqxmd.com/read/26799514/ncoa2-is-a-candidate-target-gene-of-8q-gain-associated-with-clinically-aggressive-prostate-cancer
#4
Maria P Silva, João D Barros-Silva, Joana Vieira, Susana Lisboa, Lurdes Torres, Cecília Correia, Márcia Vieira-Coimbra, Ana T Martins, Carmen Jerónimo, Rui Henrique, Paula Paulo, Manuel R Teixeira
Prostate carcinomas harboring 8q gains are associated with poor clinical outcome, but the target genes of this genomic alteration remain to be unveiled. In this study, we aimed to identify potential 8q target genes associated with clinically aggressive prostate cancer (PCa) using fluorescence in situ hybridization (FISH), genome-wide mRNA expression, and protein expression analyses. Using FISH, we first characterized the relative copy number of 8q (assessed with MYC flanking probes) of a series of 50 radical prostatectomy specimens, with available global gene expression data and typed for E26 transformation specific (ETS) rearrangements, and then compared the gene expression profile of PCa subsets with and without 8q24 gain using Significance Analysis of Microarrays...
April 2016: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/26700881/analysis-of-immune-response-markers-in-jorge-lobo-s-disease-lesions-suggests-the-occurrence-of-mixed-t-helper-responses-with-the-dominance-of-regulatory-t-cell-activity
#5
Michelle de C S Azevedo, Patricia S Rosa, Cleverson T Soares, Luciana R V Fachin, Ida Maria F D Baptista, William J Woods, Gustavo P Garlet, Ana Paula F Trombone, Andrea de F F Belone
Jorge Lobo's disease (JLD) is a chronic infection that affects the skin and subcutaneous tissues. Its etiologic agent is the fungus Lacazia loboi. Lesions are classified as localized, multifocal, or disseminated, depending on their location. Early diagnosis and the surgical removal of lesions are the best therapeutic options currently available for JLD. The few studies that evaluate the immunological response of JLD patients show a predominance of Th2 response, as well as a high frequency of TGF-β and IL-10 positive cells in the lesions; however, the overall immunological status of the lesions in terms of their T cell phenotype has yet to be determined...
2015: PloS One
https://www.readbyqxmd.com/read/26686412/transcriptome-profiling-of-human-foxp3-regulatory-t-cells
#6
Ravikiran Bhairavabhotla, Yong C Kim, Deborah D Glass, Thelma M Escobar, Mira C Patel, Rami Zahr, Cuong K Nguyen, Gokhul K Kilaru, Stefan A Muljo, Ethan M Shevach
The major goal of this study was to perform an in depth characterization of the "gene signature" of human FoxP3(+) T regulatory cells (Tregs). Highly purified Tregs and T conventional cells (Tconvs) from multiple healthy donors (HD), either freshly explanted or activated in vitro, were analyzed via RNA sequencing (RNA-seq) and gene expression changes validated using the nCounter system. Additionally, we analyzed microRNA (miRNA) expression using TaqMan low-density arrays. Our results confirm previous studies demonstrating selective gene expression of FoxP3, IKZF2, and CTLA4 in Tregs...
February 2016: Human Immunology
https://www.readbyqxmd.com/read/26437031/integrated-molecular-analysis-of-adult-t-cell-leukemia-lymphoma
#7
Keisuke Kataoka, Yasunobu Nagata, Akira Kitanaka, Yuichi Shiraishi, Teppei Shimamura, Jun-Ichirou Yasunaga, Yasushi Totoki, Kenichi Chiba, Aiko Sato-Otsubo, Genta Nagae, Ryohei Ishii, Satsuki Muto, Shinichi Kotani, Yosaku Watatani, June Takeda, Masashi Sanada, Hiroko Tanaka, Hiromichi Suzuki, Yusuke Sato, Yusuke Shiozawa, Tetsuichi Yoshizato, Kenichi Yoshida, Hideki Makishima, Masako Iwanaga, Guangyong Ma, Kisato Nosaka, Masakatsu Hishizawa, Hidehiro Itonaga, Yoshitaka Imaizumi, Wataru Munakata, Hideaki Ogasawara, Toshitaka Sato, Ken Sasai, Kenzo Muramoto, Marina Penova, Takahisa Kawaguchi, Hiromi Nakamura, Natsuko Hama, Kotaro Shide, Yoko Kubuki, Tomonori Hidaka, Takuro Kameda, Tsuyoshi Nakamaki, Ken Ishiyama, Shuichi Miyawaki, Sung-Soo Yoon, Kensei Tobinai, Yasushi Miyazaki, Akifumi Takaori-Kondo, Fumihiko Matsuda, Kengo Takeuchi, Osamu Nureki, Hiroyuki Aburatani, Toshiki Watanabe, Tatsuhiro Shibata, Masao Matsuoka, Satoru Miyano, Kazuya Shimoda, Seishi Ogawa
Adult T cell leukemia/lymphoma (ATL) is a peripheral T cell neoplasm of largely unknown genetic basis, associated with human T cell leukemia virus type-1 (HTLV-1) infection. Here we describe an integrated molecular study in which we performed whole-genome, exome, transcriptome and targeted resequencing, as well as array-based copy number and methylation analyses, in a total of 426 ATL cases. The identified alterations overlap significantly with the HTLV-1 Tax interactome and are highly enriched for T cell receptor-NF-κB signaling, T cell trafficking and other T cell-related pathways as well as immunosurveillance...
November 2015: Nature Genetics
https://www.readbyqxmd.com/read/26433257/effects-of-soluble-and-particulate-cr-vi-on-genome-wide-dna-methylation-in-human-b-lymphoblastoid-cells
#8
Jianlin Lou, Yu Wang, Junqiang Chen, Li Ju, Min Yu, Zhaoqiang Jiang, Lingfang Feng, Lingzhi Jin, Xing Zhang
Several previous studies highlighted the potential epigenetic effects of Cr(VI), especially DNA methylation. However, few studies have compared the effects of Cr(VI) on DNA methylation profiles between soluble and particulate chromate in vitro. Accordingly, Illumina Infinium Human Methylation 450K BeadChip array was used to analyze DNA methylation profiles of human B lymphoblastoid cells exposed to potassium dichromate or lead chromate, and the cell viability was also studied. Array based DNA methylation analysis showed that the impacts of Cr(VI) on DNA methylation were limited, only about 40 differentially methylated CpG sites, with an overlap of 15CpG sites, were induced by both potassium dichromate and lead chromate...
October 2015: Mutation Research. Genetic Toxicology and Environmental Mutagenesis
https://www.readbyqxmd.com/read/25780427/a-lack-of-association-between-the-ikzf2-rs12619285-polymorphism-and-coronary-heart-disease
#9
Huadan Ye, Qingxiao Hong, Yirun Li, Xuting Xu, Y I Huang, Limin Xu, Annan Zhou, Youping Deng, Shiwei Duan
The IKZF2 rs12619285 polymorphism is associated with the eosinophil count, which has multidimensional functions in the pathogenesis of coronary heart disease (CHD). The aim of the present study was to investigate the contribution of the IKZF2 rs12619285 polymorphism to the risk of CHD in a Han Chinese population. In total, 721 CHD cases and 631 non-CHD controls were recruited for an association study of the IKZF2 rs12619285 polymorphism. Genotyping was performed using the melting temperature-shift polymerase chain reaction method...
April 2015: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/25664853/musashi2-sustains-the-mixed-lineage-leukemia-driven-stem-cell-regulatory-program
#10
Sun-Mi Park, Mithat Gönen, Ly Vu, Gerard Minuesa, Patrick Tivnan, Trevor S Barlowe, James Taggart, Yuheng Lu, Raquel P Deering, Nir Hacohen, Maria E Figueroa, Elisabeth Paietta, Hugo F Fernandez, Martin S Tallman, Ari Melnick, Ross Levine, Christina Leslie, Christopher J Lengner, Michael G Kharas
Leukemia stem cells (LSCs) are found in most aggressive myeloid diseases and contribute to therapeutic resistance. Leukemia cells exhibit a dysregulated developmental program as the result of genetic and epigenetic alterations. Overexpression of the RNA-binding protein Musashi2 (MSI2) has been previously shown to predict poor survival in leukemia. Here, we demonstrated that conditional deletion of Msi2 in the hematopoietic compartment results in delayed leukemogenesis, reduced disease burden, and a loss of LSC function in a murine leukemia model...
March 2, 2015: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/25366760/microrna-network-analysis-identifies-key-micrornas-and-genes-associated-with-precancerous-lesions-of-gastric-cancer
#11
X W Wang, Y Wu, D Wang, Z F Qin
To identify potential targets for the early treatment and prevention of gastric cancer, microRNA (miRNA) expression profiles of precancerous lesions of gastric cancer were investigated. The miRNA microarray dataset GSE24839 was downloaded from Gene Expression Omnibus (GEO) and included 10 Helicobacter pylori-related gastritis samples and 10 gastric intestinal metaplasia samples. Differentially expressed miRNAs (DEMs) were screened using the Student t-test; P < 0.05 was considered to be statistically significant...
October 27, 2014: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/25252160/in-vitro-tnf-blockade-enhances-ex-vivo-expansion-of-regulatory-t-cells-in-patients-with-immune-thrombocytopenia
#12
Hui Zhong, James Bussel, Karina Yazdanbakhsh
Tumour necrosis factor-α (TNF) is an inflammatory cytokine that is elevated in a number of autoimmune diseases including immune thrombocytopenia (ITP), a bleeding disorder characterized by low platelet counts. In vitro TNF blockade increases expansion of the regulatory T cell (Treg) IKZF2 (also termed Helios) subset in T cell-monocyte cocultures from healthy donors, but its role on proliferative responses of Tregs in ITP patients, who have altered immunoregulatory compartment, remains unclear. TNF in CD4+ T cells from patients with chronic ITP were elevated and negatively correlated with peripheral Treg frequencies, suggesting a possible inhibitory effect of TNF on ITP Tregs...
January 2015: British Journal of Haematology
https://www.readbyqxmd.com/read/25062971/a-role-for-il-10-in-the-transcriptional-regulation-of-roquin-1
#13
Jeremy S Schaefer, Dina Montufar-Solis, John R Klein
Roquin-1, a RING finger E3 ubiquitin ligase, functions as a modulator of inflammation; however, nothing is known about how Rc3h1 expression is regulated. Here, we describe an opposing relationship between Roquin-1 and the IL-17 proinflammatory cytokine by demonstrating that enforced expression of Rc3h1 restricts Il17a expression, and that exposure of T cells to IL-10, a cytokine with immunosuppressive activity, increases Rc3h1 expression. Luciferase reporter assays conducted using eight transcription factor plasmids (STAT1, STAT3, STAT5, GATA2, c-Rel, IKZF1, IKZF2, and IKZF3) demonstrated that STAT1, STAT3, GATA2, and c-Rel increased Rc3h1 promoter activity, whereas IKZF2 decreased activity...
October 1, 2014: Gene
https://www.readbyqxmd.com/read/24610777/interindividual-variation-in-human-t-regulatory-cells
#14
Alessandra Ferraro, Anna Morena D'Alise, Towfique Raj, Natasha Asinovski, Roxanne Phillips, Ayla Ergun, Joseph M Replogle, Angelina Bernier, Lori Laffel, Barbara E Stranger, Philip L De Jager, Diane Mathis, Christophe Benoist
FOXP3(+) regulatory T (Treg) cells enforce immune self-tolerance and homeostasis, and variation in some aspects of Treg function may contribute to human autoimmune diseases. Here, we analyzed population-level Treg variability by performing genome-wide expression profiling of CD4(+) Treg and conventional CD4(+) T (Tconv) cells from 168 donors, healthy or with established type-1 diabetes (T1D) or type-2 diabetes (T2D), in relation to genetic and immunologic screening. There was a range of variability in Treg signature transcripts, some almost invariant, others more variable, with more extensive variability for genes that control effector function (ENTPD1, FCRL1) than for lineage-specification factors like FOXP3 or IKZF2...
March 25, 2014: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/24152290/histone-methylation-mediates-plasticity-of-human-foxp3-regulatory-t-cells-by-modulating-signature-gene-expressions
#15
COMPARATIVE STUDY
Haiqi He, Bing Ni, Yi Tian, Zhiqiang Tian, Yanke Chen, Zhengwen Liu, Xiaomei Yang, Yi Lv, Yong Zhang
CD4(+) FOXP3(+) regulatory T (Treg) cells constitute a heterogeneous and plastic T-cell lineage that plays a pivotal role in maintaining immune homeostasis and immune tolerance. However, the fate of human Treg cells after loss of FOXP3 expression and the epigenetic mechanisms contributing to such a phenotype switch remain to be fully elucidated. In the current study, we demonstrate that human CD4(+) CD25(high) CD127(low/-) Treg cells convert to two subpopulations with distinctive FOXP3(+) and FOXP3(-) phenotypes following in vitro culture with anti-CD3/CD28 and interleukin-2...
March 2014: Immunology
https://www.readbyqxmd.com/read/23334668/the-genomic-landscape-of-hypodiploid-acute-lymphoblastic-leukemia
#16
Linda Holmfeldt, Lei Wei, Ernesto Diaz-Flores, Michael Walsh, Jinghui Zhang, Li Ding, Debbie Payne-Turner, Michelle Churchman, Anna Andersson, Shann-Ching Chen, Kelly McCastlain, Jared Becksfort, Jing Ma, Gang Wu, Samir N Patel, Susan L Heatley, Letha A Phillips, Guangchun Song, John Easton, Matthew Parker, Xiang Chen, Michael Rusch, Kristy Boggs, Bhavin Vadodaria, Erin Hedlund, Christina Drenberg, Sharyn Baker, Deqing Pei, Cheng Cheng, Robert Huether, Charles Lu, Robert S Fulton, Lucinda L Fulton, Yashodhan Tabib, David J Dooling, Kerri Ochoa, Mark Minden, Ian D Lewis, L Bik To, Paula Marlton, Andrew W Roberts, Gordana Raca, Wendy Stock, Geoffrey Neale, Hans G Drexler, Ross A Dickins, David W Ellison, Sheila A Shurtleff, Ching-Hon Pui, Raul C Ribeiro, Meenakshi Devidas, Andrew J Carroll, Nyla A Heerema, Brent Wood, Michael J Borowitz, Julie M Gastier-Foster, Susana C Raimondi, Elaine R Mardis, Richard K Wilson, James R Downing, Stephen P Hunger, Mignon L Loh, Charles G Mullighan
The genetic basis of hypodiploid acute lymphoblastic leukemia (ALL), a subtype of ALL characterized by aneuploidy and poor outcome, is unknown. Genomic profiling of 124 hypodiploid ALL cases, including whole-genome and exome sequencing of 40 cases, identified two subtypes that differ in the severity of aneuploidy, transcriptional profiles and submicroscopic genetic alterations. Near-haploid ALL with 24-31 chromosomes harbor alterations targeting receptor tyrosine kinase signaling and Ras signaling (71%) and the lymphoid transcription factor gene IKZF3 (encoding AIOLOS; 13%)...
March 2013: Nature Genetics
https://www.readbyqxmd.com/read/22345564/nuclear-receptor-nr4a1-modulates-both-regulatory-t-cell-treg-differentiation-and-clonal-deletion
#17
Marlys S Fassett, Wenyu Jiang, Anna Morena D'Alise, Diane Mathis, Christophe Benoist
Immature thymocytes expressing autoreactive T-cell receptors (TCR) can adopt differing cell fates: clonal deletion by apoptosis or deviation into alternative lineages such as FoxP3(+) regulatory T cells (Treg). We revisited the role of the transcription factor Nr4a1 (Nur77), an immediate-early response gene induced by TCR engagement. Nr4a1KO mice show clear quantitative defects in antigen-induced clonal deletion. The impact of the Nr4a1 deletion is not enhanced by deletion of the proapoptotic factor Bim. In addition, Nr4a1 curtails initial differentiation into the Treg lineage in TCR transgenic mice and in nontransgenic mice...
March 6, 2012: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/21677778/helios-is-associated-with-cd4-t-cells-differentiating-to-t-helper-2-and-follicular-helper-t-cells-in-vivo-independently-of-foxp3-expression
#18
Karine Serre, Cécile Bénézech, Guillaume Desanti, Saeeda Bobat, Kai-Michael Toellner, Roger Bird, Susan Chan, Philippe Kastner, Adam F Cunningham, Ian C M Maclennan, Elodie Mohr
BACKGROUND: Although in vitro IL-4 directs CD4 T cells to produce T helper 2 (Th2)-cytokines, these cytokines can be induced in vivo in the absence of IL-4-signalling. Thus, mechanism(s), different from the in vitro pathway for Th2-induction, contribute to in vivo Th2-differentiation. The pathway for in vivo IL-4-independent Th2-differentiation has yet to be characterized. FINDINGS: Helios (ikzf2), a member of the Ikaros transcription regulator family, is expressed in thymocytes and some antigen-matured T cells as well as in regulatory T cells...
2011: PloS One
https://www.readbyqxmd.com/read/20407090/creb1-is-a-strong-genetic-predictor-of-the-variation-in-exercise-heart-rate-response-to-regular-exercise-the-heritage-family-study
#19
Tuomo Rankinen, George Argyropoulos, Treva Rice, D C Rao, Claude Bouchard
BACKGROUND: A genome-wide linkage scan identified a quantitative trait locus for exercise training-induced changes in submaximal exercise (50 W) heart rate (DeltaHR50) on chromosome 2q33.3-q34 in the HERITAGE Family Study (n=472). METHODS AND RESULTS: To fine-map the region, 1450 tag SNPs were genotyped between 205 and 215 Mb on chromosome 2. The strongest evidence of association with DeltaHR50 was observed with 2 single-nucleotide polymorphisms (SNPs) located in the 5' region of the cAMP-responsive element-binding protein 1 (CREB1) gene (rs2253206: P=1...
June 2010: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/19860791/genetic-evidence-for-a-role-of-il33-in-nasal-polyposis
#20
MULTICENTER STUDY
I D Buysschaert, V Grulois, P Eloy, M Jorissen, P Rombaux, B Bertrand, S Collet, S Bobic, S Vlaminck, P W Hellings, D Lambrechts
BACKGROUND: Little is known about the genetic factors that contribute to nasal polyposis (NP). A genome-wide association study identified 10 single nucleotide polymorphisms (SNPs) associated with eosinophilia. As eosinophils play a key role in the pathogenesis of NP, we assessed if any of these SNPs contribute to genetic susceptibility of NP. METHODS: We recruited 284 patients with NP in four participating hospitals in Belgium and 427 healthy controls, and genotyped 10 SNPs affecting eosinophilia (rs1420101 in IL1RL1, rs12619285 in IKZF2, rs4431128 in GATA2, rs4143832 in IL5, rs3184504 in SH2B3, rs2416257 in WDR36, rs2269426 in MHC, rs9494145 in MYB, rs748065 in GFRA2, and rs3939286 in IL33) using MALDI-TOF...
May 2010: Allergy
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