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https://www.readbyqxmd.com/read/29213259/characterization-of-a-suppressive-cis-acting-element-in-the-epstein-barr-virus-lmp1-promoter
#1
Masahiro Yoshida, Takayuki Murata, Keiji Ashio, Yohei Narita, Takahiro Watanabe, H M Abdullah Al Masud, Yoshitaka Sato, Fumi Goshima, Hiroshi Kimura
Latent membrane protein 1 (LMP1) is a major oncogene encoded by Epstein-Barr virus (EBV) and is essential for immortalization of B cells by the virus. Previous studies suggested that several transcription factors, such as PU.1, RBP-Jκ, NFκB, EBF1, AP-2 and STAT, are involved in LMP1 induction; however, the means by which the oncogene is negatively regulated remains unclear. Here, we introduced short mutations into the proximal LMP1 promoter that includes recognition sites for the E-box and Ikaros transcription factors in the context of EBV-bacterial artificial chromosome...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29204143/local-chromatin-features-including-pu-1-and-ikaros-binding-and-h3k4-methylation-shape-the-repertoire-of-immunoglobulin-kappa-genes-chosen-for-v-d-j-recombination
#2
Louise S Matheson, Daniel J Bolland, Peter Chovanec, Felix Krueger, Simon Andrews, Hashem Koohy, Anne E Corcoran
V(D)J recombination is essential for the generation of diverse antigen receptor (AgR) repertoires. In B cells, immunoglobulin kappa (Igκ) light chain recombination follows immunoglobulin heavy chain (Igh) recombination. We recently developed the DNA-based VDJ-seq assay for the unbiased quantitation of Igh VH and DH repertoires. Integration of VDJ-seq data with genome-wide datasets revealed that two chromatin states at the recombination signal sequence (RSS) of VH genes are highly predictive of recombination in mouse pro-B cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29177909/stem-cells-and-progenitors-in-human-peripheral-blood-get-activated-by-extremely-active-resveratrol-xar%C3%A2
#3
Vinaykumar Tripathi, Sagar Chhabria, Vaibhav Jadhav, Deepa Bhartiya, Ashish Tripathi
Resveratrol generated enormous interest as it improved functions of multiple organs and could delay aging in animal models. However, basic mechanism of action was not understood and due to poor bioavailability, it has failed to enter the market. A highly active nano-formulation of resveratrol (XAR™) with enhanced bioavailability is now available. Present study was undertaken to evaluate its effects on stem cells biology in the human peripheral blood. Twelve healthy participants were enrolled of which five received XAR™, five were age-matched placebo controls and two were 76 and 85 years old...
November 24, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/29168113/dynamics-of-bone-marrow-vsels-and-hscs-in-response-to-treatment-with-gonadotropin-and-steroid-hormones-during-pregnancy-and-evidence-to-support-their-asymmetric-symmetric-cell-divisions
#4
Ranita Ganguly, Sidhanath Metkari, Deepa Bhartiya
Gender plays an important role in the incidence of hematological malignancies and recently hematopoietic stem cells (HSCs) were found to proliferate more in females that gets further augmented during pregnancy. It was suggested that since basal numbers of HSCs remain the same in both sexes, possibly HSCs in females undergo increased self-renewal and apoptosis. Then how is self-renewal of stem cells regulated in males? More important, do HSCs undergo asymmetric cell divisions (ACD) or a more primitive population of pluripotent, very small embryonic-like stem cells (VSELs) undergo ACD to self-renew and specify into HSCs? Lot more clarity is required on the bone marrow stem cells biology...
November 22, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/29107383/alteration-in-ikaros-expression-promotes-b-1-cell-differentiation-into-phagocytes
#5
Vivian Cristina de Oliveira, Ana Clara Pires Sodré, Caio Perez Gomes, Nilmar Silvio Moretti, João Bosco Pesquero, Ana Flavia Popi
Ikaros is a broad transcription factor pointed as a critical regulator of lymphocyte development. Recent reports have emphasized that distinct isoforms of Ikaros control the dichotomy of the hematopoietic system into lymphoid and myeloid lineages. In addition, expression of dominant-negative isoforms of Ikaros is linked to abnormal hematopoiesis, which could culminate in hematological disorders due to loss of function of the protein. B-1 cells are an intriguing subtype of B-lymphocytes that preserves some myeloid characteristics...
October 6, 2017: Immunobiology
https://www.readbyqxmd.com/read/29042995/overexpression-of-dominant-negative-ikaros-6-isoform-is-associated-with-resistance-to-tkis-in-patients-with-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia
#6
Changfeng Shao, Jie Yang, Yirong Kong, Cong Cheng, Wei Lu, Hongzai Guan, Haiyan Wang
The clinical significance of the dominant-negative Ikaros 6 (DN-IK6) in the treatment of patients with Philadelphia-positive acute lymphoblastic leukemia (Ph(+)-ALL) with tyrosine kinase inhibitors (TKIs) remains elusive. In the present study, it was demonstrated that DN-IK6 was overexpressed in B-cell (B)-ALL cases compared with T cell-ALL cases at the mRNA and protein levels. Furthermore, nucleotide sequencing revealed that DN-IK6 was due to the deletion of IKAROS family zinc finger 1 exons 4-7. The outcome of patients with Ph(+)-B-ALL with DN-IK6, and treated with TKIs and hyper-cyclophosphamide/vincristine/doxorubicin/dexamethasone regimen were restrospectively evaluated in a 2 year follow-up...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28994305/plant-homeodomain-finger-protein-2-as-a-novel-ikaros-target-in-acute-lymphoblastic-leukemia
#7
Zheng Ge, Yan Gu, Qi Han, Justin Sloane, Qinyu Ge, Goufeng Gao, Jinlong Ma, Huihui Song, Jiaojiao Hu, Baoan Chen, Sinisa Dovat, Chunhua Song
AIM: Clinical significance of plant homeodomain finger 2 (PHF2) expressions is explored in acute lymphoblastic leukemia (ALL) patients. METHODS: mRNA level was examined by qPCR. The retroviral gene expression, shRNA knockdown and chromatin-immunoprecipitation are used to observe IKAROS regulation on PHF2 transcription. RESULTS: PHF2 expression is significantly reduced in subsets of ALL patients, and PHF2 (low) expression correlates with leukemia cell proliferation and an elevation of several poor prognostic markers in B-cell ALL...
October 10, 2017: Epigenomics
https://www.readbyqxmd.com/read/28963879/accuracy-of-serum-ige-concentrations-and-papule-diameter-in-the-diagnosis-of-cow-s-milk-allergy
#8
Jackeline M Franco, Ana Paula S G Pinheiro, Sarah C F Vieira, Íkaro Daniel C Barreto, Ricardo Q Gurgel, Renata R Cocco, Dirceu Solé
OBJECTIVE: To compare serum concentrations of specific IgE and mean papule diameters induced in the immediate skin reactivity test with cow's milk (CM) and its fractions with results of the oral challenge test (OCT), and to establish cutoff points capable of predicting clinical reactivity to CM in patients treated at a referral service. METHODS: One hundred and twenty-two children (median of 17 months) with a history of immediate reactions to CM and presence of specific IgE for CM and/or its fractions (positive skin and/or IgE serum tests) were submitted to open OCT with CM...
September 28, 2017: Jornal de Pediatria
https://www.readbyqxmd.com/read/28927821/a-novel-ikaros-haploinsufficiency-kindred-with-unexpectedly-late-and-variable-b-cell-maturation-defects
#9
Delfien J Bogaert, Hye Sun Kuehn, Carolien Bonroy, Katherine R Calvo, Joke Dehoorne, Arnaud V Vanlander, Marieke De Bruyne, Urszula Cytlak, Venetia Bigley, Frans De Baets, Elfride De Baere, Sergio D Rosenzweig, Filomeen Haerynck, Melissa Dullaers
We report on the first truncating IKZF1 mutation associated with IKAROS haploinsufficiency and illustrate an unexpectedly late and variable block in central and peripheral B cell development in two patients and their asymptomatic mother.
September 16, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28927157/selected-mirna-levels-are-associated-with-ikzf1-microdeletions-in-pediatric-acute-lymphoblastic-leukemia
#10
J Krzanowski, J Madzio, A Pastorczak, A Tracz, M Braun, J Tabarkiewicz, A Pluta, W Młynarski, I Zawlik
The clinical outcome of children with high-risk relapsed B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is poor. The present study assessed the utility and prognostic value of selected microRNA (miRNA/miR) in BCP-ALL. The changes in the expression levels of these miRNAs regarding known gene lesions affecting lymphoid development [early B-cell factor 1 (EBF1), ETS variant 6 (ETV6), IKAROS family zinc finger 1 (IKZF1), paired box 5 (PAX5), cyclin dependent kinase inhibitor (CDKN) 2A/CDKN2B, retinoblastoma 1 (RB1), pseudoautosomal region 1 (PAR1), B-cell translocation gene 1 protein (BTG1)] were analyzed...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28927072/arsenic-trioxide-potentiates-sensitivity-of-multiple-myeloma-cells-to-lenalidomide-by-upregulating-cereblon-expression-levels
#11
Yuan Jian, Wen Gao, Chuanying Geng, Huixing Zhou, Yun Leng, Yanchen Li, Wenming Chen
The mechanism of the anti-myeloma effect of the immunomodulatory drug lenalidomide relies upon the binding of lenalidomide or an analogue to cereblon (CRBN) ubiquitin ligase, which inhibits it and results in the degradation of Ikaros-family zinc finger proteins 1 and 3 (IKZF1 and IKZF3). To determine whether the traditional Chinese medicine arsenic trioxide, could potentiate sensitivity of multiple myeloma (MM) cells to lenalidomide and identify the mechanism by which this happens, the present study investigated how arsenic trioxide affected CRBN on MM cell lines and examined the anti-myeloma effect and mechanism in the combination of arsenic trioxide and lenalidomide...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28919299/the-retrotransposon-gag-domain-containing-protein-rgag4-is-an-ikaros-target-in-the-pituitary
#12
Zhongyi Shen, Sylvia L Asa, Shereen Ezzat
Previous studies have established the common and critical involvement of the zinc finger protein Ikaros in lymphoid and pituitary cell development and expansion. Key to the assembly of several transcriptional networks, we have demonstrated up-regulation of Ikaros and its interacting partner the C-terminal Binding Protein (CtBP) in response to hypoxia. This prompted us to explore common transcriptional targets using a chromatin immunoprecipitate (ChIP) screen of DNA from pituitary corticotroph cells. This strategy yielded a finite list of targets common to both transcription factors that included the metalloprotease ADAMTS10...
September 14, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28914974/mucocutaneous-inflammation-in-the-ikaros-family-zinc-finger-1-ikzf1-keratin-5-specifc-transgenic-mice
#13
Mayumi Ueta, Junji Hamuro, Hiromi Nishigaki, Naomi Nakamura, Katsuhiko Shinomiya, Katsura Mizushima, Yuki Hitomi, Risa Tamagawa-Mineoka, Norihiko Yokoi, Yuji Naito, Katsushi Tokunaga, Norito Katoh, Chie Sotozono, Shigeru Kinoshita
BACKGROUND: Our genome-wide association study documented an association between cold medicine related Stevens-Johnson syndrome / toxic epidermal necrolysis (CM-SJS/TEN) and Ikaros Family Zinc Finger 1 (IKZF1). Few studies examined biological and pathological functions of IKZF1 in mucosal immunity. We hypothesized that IKZF1 contributes to the mucocutaneous inflammation. METHODS: Human skin and conjunctival tissues were obtained for immunohistological studies. Primary human conjunctival epithelial cells (PHCjECs) and adult human epidermal keratinocytes (HEKa) also used for gene expression analysis...
September 15, 2017: Allergy
https://www.readbyqxmd.com/read/28893618/lenalidomide-modulates-gene-expression-in-human-abc-dlbcl-cells-by-regulating-ikaros-interaction-with-an-intronic-control-region-of-spib
#14
Lauren A Solomon, Carolina R Batista, Rodney P DeKoter
Activated B-cell diffuse large B-cell lymphoma (ABC-DLBCL) is associated with a poor prognosis compared with other DLBCL types and therefore represents a top priority for developing novel therapies. Lenalidomide, an immunomodulatory drug in trials for treatment of ABC-DLBCL, targets the transcription factor IKAROS for degradation by the cereblon E3 ubiquitin ligase complex. In this study, we investigated whether the gene encoding the transcription factor SPI-B is a target of IKAROS. Using cultured ABC-DLBCL cell lines, we found that high levels of SPI-B expression conferred resistance to lenalidomide...
December 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28881793/lenalidomide-increases-human-dendritic-cell-maturation-in-multiple-myeloma-patients-targeting-monocyte-differentiation-and-modulating-mesenchymal-stromal-cell-inhibitory-properties
#15
Federica Costa, Rosanna Vescovini, Marina Bolzoni, Valentina Marchica, Paola Storti, Denise Toscani, Fabrizio Accardi, Laura Notarfranchi, Benedetta Dalla Palma, Cristina Manferdini, Sabrina Manni, Giannalisa Todaro, Gina Lisignoli, Francesco Piazza, Franco Aversa, Nicola Giuliani
The use of Lenalidomide (LEN), to reverse tumor-mediated immune suppression and amplify multiple myeloma-specific immunity is currently being explored. Particularly, LEN effects on dendritic cells (DCs) are still unclear. In this study, we investigated the potential effect of LEN on DC differentiation and activity. DCs were differentiated either from CD14(+) cells obtained from patients with multiple myeloma or from a human monocytic cell line. LEN, at the concentration range reached in vivo, significantly increased the median intensity expression of HLA-DR, CD86 and CD209 by DCs derived from both bone marrow and peripheral myeloma monocytes and enhanced the production of Interleukin-8, C-C motif chemokine ligand (CCL) 2, CCL5 and tumor necrosis factor-α...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28846748/plasmacytoid-dendritic-cells-and-rna-containing-immune-complexes-drive-expansion-of-peripheral-b-cell-subsets-with-an-sle-like-phenotype
#16
Olof Berggren, Niklas Hagberg, Andrei Alexsson, Gert Weber, Lars Rönnblom, Maija-Leena Eloranta
BACKGROUND: Hyperactive B cells and a continuous interferon (IFN)-α production by plasmacytoid dendritic cells (pDCs) play a key role in systemic lupus erythematosus (SLE). We asked whether the interaction between B cells and pDCs stimulated with RNA-containing immune complexes affects peripheral B cell subsets. METHODS: B cells and pDCs were isolated from blood of healthy individuals and stimulated with immune complexes consisting of SLE-IgG and U1snRNP (RNA-IC)...
2017: PloS One
https://www.readbyqxmd.com/read/28758047/the-role-of-the-ikaros-family-of-transcription-factors-in-regulatory-t-cell-development-and-function
#17
Amara Seng, Thomas M Yankee
Regulatory T (Treg) cells are a subset of immune cells that maintain homeostasis by promoting immune tolerance and suppressing the immune response via a variety of mechanisms such as secreting cytokines, killing reactive immune cells, and inducing anergy. Dysfunction of Treg cells has been implicated in inflammatory diseases such as autoimmunity and transplant rejection. Conversely, too many or hyperresponsive Treg cells has been observed in cancer and chronic infections. Treg cells have proven to be difficult to study as there are no definitive Treg surface markers...
April 2017: Journal of Clinical & Cellular Immunology
https://www.readbyqxmd.com/read/28751559/loss-of-function-but-not-dominant-negative-intragenic-ikzf1-deletions-are-associated-with-an-adverse-prognosis-in-adult-bcr-abl-negative-acute-lymphoblastic-leukemia
#18
Benjamin Kobitzsch, Nicola Gökbuget, Stefan Schwartz, Richard Reinhardt, Monika Brüggemann, Andreas Viardot, Ralph Wäsch, Michael Starck, Eckhard Thiel, Dieter Hoelzer, Thomas Burmeister
Genetic alterations of the transcription factor IKZF1 ("IKAROS") are detected in around 15-30% of cases of BCR-ABL-negative B-cell precursor acute lymphoblastic leukemia. Different types of intragenic deletions have been observed, resulting in a functionally inactivated allele ("loss-of-function") or in "dominant-negative" isoforms. The prognostic impact of these alterations especially in adult acute lymphoblastic leukemia is not well defined. We analyzed 482 well-characterized cases of adult BCR-ABL-negative B-precursor acute lymphoblastic leukemia uniformly treated in the framework of the GMALL studies and detected IKZF1 alterations in 128 cases (27%)...
October 2017: Haematologica
https://www.readbyqxmd.com/read/28751557/the-bet-bromodomain-inhibitor-cpi203-improves-lenalidomide-and-dexamethasone-activity-in-in-vitro-and-in-vivo-models-of-multiple-myeloma-by-blockade-of-ikaros-and-myc-signaling
#19
Tania Díaz, Vanina Rodríguez, Ester Lozano, Mari-Pau Mena, Marcos Calderón, Laura Rosiñol, Antonio Martínez, Natalia Tovar, Patricia Pérez-Galán, Joan Bladé, Gaël Roué, Carlos Fernández de Larrea
Most patients with multiple myeloma treated with current therapies, including immunomodulatory drugs, eventually develop relapsed/refractory disease. Clinical activity of lenalidomide relies on degradation of Ikaros and the consequent reduction in IRF4 expression, both required for myeloma cell survival and involved in the regulation of MYC transcription. Thus, we sought to determine the combinational effect of an MYC-interfering therapy with lenalidomide/dexamethasone. We analyzed the potential therapeutic effect of the combination of the BET bromodomain inhibitor CPI203 with the lenalidomide/dexamethasone regimen in myeloma cell lines...
October 2017: Haematologica
https://www.readbyqxmd.com/read/28707666/-identification-of-proteins-associated-with-transcription-factors-hoxa9-and-e2a-pbx1-by-tandem-affinity-purification
#20
E A Shestakova, M Boutin, S Bourassa, E Bonneil, J J Bijl
Chimeric transcription factor E2A-PBX1 induces the development of acute lymphoblastic B-cell leukemia in children. Using a transgenic mouse model, we previously demonstrated that homeobox (HOX) gene HOXA9 genetically interact with E2A-PBX1 gene in the development of B-cell leukemia in mice. HOXA9 itself is a potent oncogene resulting in myeloid leukemia when overexpressed, which is strongly accelerated by its collaborator Meis1. HOX, PBX1 and MEIS1 proteins have been shown to form hetero dimeric or trimeric complexes in different combinations...
May 2017: Molekuliarnaia Biologiia
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