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https://www.readbyqxmd.com/read/29166413/comprehensive-molecular-profiling-of-718-multiple-myelomas-reveals-significant-differences-in-mutation-frequencies-between-african-and-european-descent-cases
#1
Zarko Manojlovic, Austin Christofferson, Winnie S Liang, Jessica Aldrich, Megan Washington, Shukmei Wong, Daniel Rohrer, Scott Jewell, Rick A Kittles, Mary Derome, Daniel Auclair, David Wesley Craig, Jonathan Keats, John D Carpten
Multiple Myeloma (MM) is a plasma cell malignancy with significantly greater incidence and mortality rates among African Americans (AA) compared to Caucasians (CA). The overall goal of this study is to elucidate differences in molecular alterations in MM as a function of self-reported race and genetic ancestry. Our study utilized somatic whole exome, RNA-sequencing, and correlated clinical data from 718 MM patients from the Multiple Myeloma Research Foundation CoMMpass study Interim Analysis 9. Somatic mutational analyses based upon self-reported race corrected for ancestry revealed significant differences in mutation frequency between groups...
November 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29158347/pillars-article-requirement-for-the-transcription-factor-lsirf-irf4-for-mature-b-and-t-lymphocyte-function-science-1997-275-540-543
#2
Hans-Willi Mittrücker, Toshifumi Matsuyama, Alex Grossman, Thomas M Kündig, Julia Potter, Arda Shahinian, Andrew Wakeham, Bruce Patterson, Pamela S Ohashi, Tak W Mak
No abstract text is available yet for this article.
December 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29158346/critical-functions-of-irf4-in-b-and-t-lymphocytes
#3
James Hagman
No abstract text is available yet for this article.
December 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29156727/bone-marrow-irf4-level-in-multiple-myeloma-an-indicator-of-peripheral-blood-th17-and-disease
#4
Hua Bai, Shuang Wu, Rong Wang, Ji Xu, Lijuan Chen
Interferon regulator factor 4 (IRF4) is characterized to be a member of interferon regulatory family, which is predominantly expressed in bone marrow plasma cells of patients with multiple myeloma (MM). Recent studies indicated IRF4 is critical for T-help cells (Th17) differentiation and interleukin-17 (IL-17) secretion. Here, a total of 58 MM patients were enrolled in this study, the proportions of Th17 cells and T regulatory (Treg) cells in peripheral blood mononuclear cells (PBMCs) were determined by flow cytometric analysis...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29154209/external-signals-regulate-germinal-center-fate-determining-transcription-factors-in-the-a20-lymphoma-cell-line
#5
Juan Feng, Xin Liu, Xingya Ni, Hai Qi
Due to the apoptosis-prone nature of primary germinal center B (GCB) cells, it remains a huge challenge to dissect signals that guide their differentiation towards memory B cells and plasma cells in vitro. Here we show that the murine lymphoma cell line A20 resembles primary GCB cells in expression of GC-specific surface markers and the master transcription factor BCL6 and may serve as a useful system to model certain GCB cell behaviors in vitro. Using these cells, we found that both CD40 and B cell receptor (BCR) signaling are able to drive BCL6 downregulation, which is a prerequisite of post-GC B-cell differentiation...
November 16, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29131464/interferon-regulatory-factor-4-5-signaling-impacts-on-microglial-activation-after-ischemic-stroke-in-mice
#6
Abdullah Al Mamun, Anjali Chauhan, Haifu Yu, Yan Xu, Romana Sharmeen, Fudong Liu
Microglial activation is a key element in initiating and perpetuating inflammatory responses to stroke. Interferon regulatory factor 5 (IRF5) and IRF4 signaling have been found critical in mediating macrophage pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes respectively in peripheral inflammation. We hypothesize that the IRF5/4 regulatory axis also mediates microglial activation after stroke. C57BL6 mice of 8-12 weeks were subject to a 90-minute middle cerebral artery occlusion and the brains evaluated at 24h, 3d, 10d and 30d after reperfusion...
November 13, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29122991/maternal-embryonic-leucine-zipper-kinase-is-a-novel-target-for-proliferation-associated-high-risk-myeloma
#7
Arnold Bolomsky, Roy Heusschen, Karin Schlangen, Kathrin Stangelberger, Joséphine Muller, Wolfgang Schreiner, Niklas Zojer, Jo Caers, Heinz Ludwig
Treatment of high-risk patients is a major challenge in multiple myeloma. This is especially true for patients assigned to the gene-expression-profiling defined proliferation subgroup. Although recent efforts have identified some key players of proliferative myeloma, genetic interactions and players that can be targeted with clinically effective drugs have to be identified to overcome the poor prognosis of these patients. We therefore examined maternal embryonic leucine zipper kinase (MELK) for its implications in hyper-proliferative myeloma and analysed the activity of the MELK inhibitor OTSSP167 in vitro and in vivo...
November 9, 2017: Haematologica
https://www.readbyqxmd.com/read/29122756/foxp1-expression-is-a-prognostic-biomarker-in-follicular-lymphoma-treated-with-rituximab-containing-regimens
#8
Anja Mottok, Vindi Jurinovic, Pedro Farinha, Andreas Rosenwald, Ellen Leich, German Ott, Heike Horn, Wolfram Klapper, Michael Boesl, Wolfgang Hiddemann, Christian Steidl, Joseph M Connors, Laurie H Sehn, Randy D Gascoyne, Eva Hoster, Oliver Weigert, Robert Kridel
Follicular lymphoma (FL) is a clinically and molecularly highly heterogeneous disease, yet prognostication relies predominantly on clinical tools. We recently demonstrated that integration of mutation status of seven genes, including EZH2 and MEF2B, improves risk stratification. We mined gene expression data to uncover genes that are differentially expressed in EZH2- and MEF2B-mutated cases. We focused on FOXP1 and assessed its protein expression by immunohistochemistry (IHC) in a total of 763 tissue biopsies...
November 9, 2017: Blood
https://www.readbyqxmd.com/read/29097500/a-bio-clinical-prognostic-model-using-myc-and-bcl2-predicts-outcome-in-relapsed-refractory-diffuse-large-b-cell-lymphoma
#9
Mark Bosch, Ariz Akhter, Bingshu E Chen, Adnan Mansoor, David Lebrun, David Good, Michael Crump, Lois Shepherd, David W Scott, Douglas A Stewart
The objective of this study was to create a bio-clinical model, based on clinical and molecular predictors of event-free and overall survival for relapsed/refractory diffuse large B-cell lymphoma patients treated on the Canadian Cancer Trials Group LY12 prospective study. Sufficient histologic material was available for 91 cases to create tissue microarrays and perform immunohistochemistry staining for CD10, BCL6, MUM1/IRF4, FOXP1, LMO2, BCL2, MYC, P53 and pySTAT3 expression. 67 cases had material sufficient for fluorescent in-situ hybridization for MYC and BCL2...
November 2, 2017: Haematologica
https://www.readbyqxmd.com/read/29070116/-effect-of-b-cell-differentiation-markers-on-the-prognosis-of-primary-central-nervous-system-lymphoma
#10
Xiang-Lei Chen, Xiao-Yun Li, Wei Wang
OBJECTIVE: To investigate the value of B-cell differentiation markers in prognosis evaluation of 119 patients with primary CNS lymphoma(PCNSL). METHODS: The expressions of BCL-2, BCL-6, CD10 and MUM1/IRF4 protein were determined by immunohistochemistry, and their relationship with the prognosis of primary central nervous system lymphoma was analyzed. RESULTS: Univariate analysis showed that BCL-6 positive means shorter PFS (P=0.047) and OS (P=0...
October 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29054828/cloning-and-expression-study-of-an-irf4a-gene-and-its-two-transcript-variants-in-turbot-scophthalmus-maximus
#11
Song Li, Guobin Hu, Zhipeng Chen, Lianfei Song, Guanjie Wang, Dahai Liu, Qiuming Liu
Interferon regulatory factor 4 (IRF4) is known to be involved in antiviral response as well as regulation of functional and developmental processes in lymphomyeloid cell lineages in mammals. In this study, the gene of IRF4a and its two transcript variants (named IRF4a1 and -2) were cloned from turbot, Scophthalmus maximus, the tissue distributions and in vivo immune responsive expression patterns of the two transcripts were subsequently examined. The Scophthalmus maximus (Sm)IRF4a gene is 8367 nucleotide (nt) in length, consisting of eight exons and seven introns...
October 18, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29054604/susceptibility-loci-associated-cutaneous-squamous-cell-carcinoma-invasiveness
#12
Wei Wang, Eric Jorgenson, Alice S Whittemore, Maryam M Asgari
Genome-wide association studies (GWAS) have identified genetic loci associated with cutaneous squamous cell carcinoma (cSCC) risk, but single nucleotide polymorphisms (SNP) associations with cSCC invasiveness have not been investigated. We examined associations between cSCC invasiveness and 23 reported SNPs among 67,833 non-Hispanic white subjects. Additionally, we performed a genome-wide scan and identified one SNP with significantly different frequencies in 5,724 subjects with at least one invasive tumor and 1,943 subjects with in-situ tumors only...
October 17, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29045832/utx-kdm6a-loss-enhances-the-malignant-phenotype-of-multiple-myeloma-and-sensitizes-cells-to-ezh2-inhibition
#13
Teresa Ezponda, Daphné Dupéré-Richer, Christine M Will, Eliza C Small, Nobish Varghese, Tej Patel, Behnam Nabet, Relja Popovic, Jon Oyer, Marinka Bulic, Yupeng Zheng, Xiaoxiao Huang, Mrinal Y Shah, Sayantan Maji, Alberto Riva, Manuela Occhionorelli, Giovanni Tonon, Neil Kelleher, Jonathan Keats, Jonathan D Licht
Loss or inactivation of the histone H3K27 demethylase UTX occurs in several malignancies, including multiple myeloma (MM). Using an isogenic cell system, we found that loss of UTX leads to deactivation of gene expression ultimately promoting the proliferation, clonogenicity, adhesion, and tumorigenicity of MM cells. Moreover, UTX mutant cells showed increased in vitro and in vivo sensitivity to inhibition of EZH2, a histone methyltransferase that generates H3K27me3. Such sensitivity was related to a decrease in the levels of IRF4 and c-MYC and an activation of repressors of IRF4 characteristic of germinal center B cells such as BCL6 and IRF1...
October 17, 2017: Cell Reports
https://www.readbyqxmd.com/read/29024646/the-epstein-barr-virus-regulome-in-lymphoblastoid-cells
#14
Sizun Jiang, Hufeng Zhou, Jun Liang, Catherine Gerdt, Chong Wang, Liangru Ke, Stefanie C S Schmidt, Yohei Narita, Yijie Ma, Shuangqi Wang, Tyler Colson, Benjamin Gewurz, Guoliang Li, Elliott Kieff, Bo Zhao
Epstein-Barr virus (EBV) transforms B cells to continuously proliferating lymphoblastoid cell lines (LCLs), which represent an experimental model for EBV-associated cancers. EBV nuclear antigens (EBNAs) and LMP1 are EBV transcriptional regulators that are essential for LCL establishment, proliferation, and survival. Starting with the 3D genome organization map of LCL, we constructed a comprehensive EBV regulome encompassing 1,992 viral/cellular genes and enhancers. Approximately 30% of genes essential for LCL growth were linked to EBV enhancers...
October 11, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/29023386/the-immunogenicity-of-branded-and-biosimilar-infliximab-in-rheumatoid-arthritis-according-to-th9-related-responses
#15
Rossella Talotta, Angela Berzi, Andrea Doria, Alberto Batticciotto, Maria Chiara Ditto, Fabiola Atzeni, Piercarlo Sarzi-Puttini, Daria Trabattoni
Our objective was to evaluate the immunogenicity of branded and biosimilar infliximab by detecting changes in T-helper-9 (Th9) percentages induced by an in vitro stimulation test. METHODS: Peripheral blood mononuclear cells collected from 55 consecutive rheumatoid arthritis (RA) outpatients (15 drug free, 20 successfully treated with branded infliximab, 20 branded infliximab inadequate responders) and 10 healthy controls were cultured, with or without 50 μg/mL of infliximab originator (Remicade(®)) or 50 μg/mL of infliximab biosimilar (Remsima(®)) for 18 h...
October 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29022922/rankl-mediated-harmonious-dialogue-between-fetus-and-mother-guarantees-smooth-gestation-by-inducing-decidual-m2-macrophage-polarization
#16
Yu-Han Meng, Wen-Jie Zhou, Li-Ping Jin, Li-Bing Liu, Kai-Kai Chang, Jie Mei, Hui Li, Jian Wang, Da-Jin Li, Ming-Qing Li
Decidual macrophages (dMϕ) contribute to maternal-fetal tolerance. However, the mechanism of dMϕ differentiation during pregnancy is still largely unknown. Here, we report that receptor activator for nuclear factor-κ B ligand (RANKL), secreted by human embryonic trophoblasts and maternal decidual stromal cells (DSCs), polarizes dMϕ toward a M2 phenotype. This polarization is mediated through activation of Akt/signal transducer and activator of transcription 6 (STAT6) signaling, which is associated with the upregulation of histone H3 lysine-27 demethylase Jmjd3 and IRF4 in dMϕ...
October 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28993609/transcription-factor-foxo1-is-essential-for-il-9-induction-in-t-helper-cells
#17
Sakshi Malik, Srikanth Sadhu, Srikanth Elesela, Ramendra Pati Pandey, Amanpreet Singh Chawla, Deepak Sharma, Lipsa Panda, Deepak Rathore, Balram Ghosh, Vineet Ahuja, Amit Awasthi
Interleukin 9 (IL-9)-producing helper T (Th9) cells have a crucial function in allergic inflammation, autoimmunity, immunity to extracellular pathogens and anti-tumor immune responses. In addition to Th9, Th2, Th17 and Foxp3(+) regulatory T (Treg) cells produce IL-9. A transcription factor that is critical for IL-9 induction in Th2, Th9 and Th17 cells has not been identified. Here we show that the forkhead family transcription factor Foxo1 is required for IL-9 induction in Th9 and Th17 cells. We further show that inhibition of AKT enhances IL-9 induction in Th9 cells while it reciprocally regulates IL-9 and IL-17 in Th17 cells via Foxo1...
October 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28977998/nkl-homeobox-gene-msx1-acts-like-a-tumor-suppressor-in-nk-cell-leukemia
#18
Stefan Nagel, Claudia Pommerenke, Corinna Meyer, Maren Kaufmann, Roderick A F MacLeod, Hans G Drexler
NKL homeobox gene MSX1 is physiologically expressed in lymphoid progenitors and subsequently downregulated in developing T- and B-cells. In contrast, elevated expression levels of MSX1 persist in mature natural killer (NK)-cells, indicating a functional role in this compartment. While T-cell acute lymphoblastic leukemia (T-ALL) subsets exhibit aberrant overexpression of MSX1, we show here that in malignant NK-cells the level of MSX1 transcripts is aberrantly downregulated. Chromosomal deletions at 4p16 hosting the MSX1 locus have been described in NK-cell leukemia patients...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28944344/irf4-couples-anabolic-metabolism-to-th1-cell-fate-determination
#19
Radomir Kratchmarov, Simone A Nish, Wen-Hsuan W Lin, William C Adams, Yen-Hua Chen, Bonnie Yen, Nyanza J Rothman, Ulf Klein, Steven L Reiner
Anabolic metabolism in lymphocytes promotes plasmablast and cytotoxic T cell differentiation at the expense of self-renewal. Heightened expression and function of the transcription factor IFN regulatory factor 4 (IRF4) accompany enhanced anabolic induction and full commitment to functional differentiation in B cells and CD8(+) T cells. In this study, we used a genetic approach to determine whether IRF4 plays an analogous role in Th1 cell induction. Our findings indicate that IRF4 promotes determined Th1 cell differentiation in tandem with anabolic metabolism of CD4(+) T cells...
September 1, 2017: Immunohorizons
https://www.readbyqxmd.com/read/28930664/aryl-hydrocarbon-receptor-controls-monocyte-differentiation-into-dendritic-cells-versus-macrophages
#20
Christel Goudot, Alice Coillard, Alexandra-Chloé Villani, Paul Gueguen, Adeline Cros, Siranush Sarkizova, Tsing-Lee Tang-Huau, Mylène Bohec, Sylvain Baulande, Nir Hacohen, Sebastian Amigorena, Elodie Segura
After entering tissues, monocytes differentiate into cells that share functional features with either macrophages or dendritic cells (DCs). How monocyte fate is directed toward monocyte-derived macrophages (mo-Macs) or monocyte-derived DCs (mo-DCs) and which transcription factors control these differentiation pathways remains unknown. Using an in vitro culture model yielding human mo-DCs and mo-Macs closely resembling those found in vivo in ascites, we show that IRF4 and MAFB were critical regulators of monocyte differentiation into mo-DCs and mo-Macs, respectively...
September 19, 2017: Immunity
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