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Bcl6

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https://www.readbyqxmd.com/read/28544233/bcl6-overexpression-alters-gene-expression-profile-in-a-myeloma-cell-line-and-is-associated-with-decreased-dna-damage-response
#1
Kenichi Tahara, Makiko Takizawa, Arito Yamane, Yohei Osaki, Takuma Ishizaki, Takeki Mitsui, Akihiko Yokohama, Takayuki Saitoh, Norifumi Tsukamoto, Morio Matsumoto, Hirokazu Murakami, Yoshihisa Nojima, Hiroshi Handa
BCL6 attenuates DNA damage response (DDR) through gene repression and facilitates tolerance to genomic instability during immunoglobulin affinity maturation in germinal center (GC) B cells. Although BCL6 expression is repressed through normal differentiation of GC B cells into plasma cells, a recent study showed the ectopic expression of BCL6 in primary multiple myeloma (MM) cells. However, the functional roles of BCL6 in MM cells are largely unknown. Here, we report that overexpression of BCL6 in a MM cell line, KMS12PE, induced transcriptional repression of ataxia telangiectasia mutated (ATM), a DDR signaling kinase, which was associated with a reduction in γH2AX formation after DNA damage...
May 23, 2017: Cancer Science
https://www.readbyqxmd.com/read/28525305/clinical-impact-of-the-cell-of-origin-classification-and-the-myc-bcl2-dual-expresser-status-in-diffuse-large-b-cell-lymphoma-treated-within-prospective-clinical-trials-of-the-german-high-grade-non-hodgkin-s-lymphoma-study-group
#2
Annette M Staiger, Marita Ziepert, Heike Horn, David W Scott, Thomas F E Barth, Heinz-Wolfram Bernd, Alfred C Feller, Wolfram Klapper, Monika Szczepanowski, Michael Hummel, Harald Stein, Dido Lenze, Martin-Leo Hansmann, Sylvia Hartmann, Peter Möller, Sergio Cogliatti, Georg Lenz, Lorenz Trümper, Markus Löffler, Norbert Schmitz, Michael Pfreundschuh, Andreas Rosenwald, German Ott
Purpose To explore the prognostic impact and interdependence of the cell-of-origin (COO) classification, dual expression (DE) of MYC and BCL2 proteins, and MYC, BCL2, and BCL6 translocations in two prospectively randomized clinical trials of patients with diffuse large B-cell lymphoma (DLBCL). Patients and Methods Overall, 452 formalin-fixed paraffin-embedded samples from two prospective, randomized DLBCL trials (RICOVER-60, prospective, randomized study for patients > 60 years, all IPI groups; and R-MegaCHOEP, prospective, randomized study for patients ≤ 60 years with age-adjusted IPI 2,3) of the German High-Grade Non-Hodgkin Lymphoma Study Group were analyzed with the Lymph2Cx assay for COO classification, with immunohistochemistry for MYC and BCL2, and with fluorescent in situ hybridization for MYC, BCL2, and BCL6 rearrangements...
May 19, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28511943/relationship-between-soluble-cd25-and-gene-expression-in-healthy-individuals-and-patients-with-multiple-sclerosis
#3
Sophie Buhelt, Rikke Lenhard Ratzer, Jeppe Romme Christensen, Lars Börnsen, Finn Sellebjerg, Helle Bach Søndergaard
Genome wide association studies and fine mapping has established a firm link between the IL2RA gene, encoding the interleukin-2 receptor α-chain CD25, and susceptibility to multiple sclerosis (MS). We hypothesized that gene expression in peripheral blood mononuclear cells (PBMCs) from healthy controls (HCs) and MS patients are associated with IL2RA SNP rs2104286 and that gene expression levels correlate with soluble CD25 (sCD25) concentrations - that are affected by rs2104286. We used the Affymetrix Human Gene ST 1...
May 13, 2017: Cytokine
https://www.readbyqxmd.com/read/28504205/comparison-of-clinicopathologic-characteristics-of-gastric-follicular-lymphomas-and-duodenal-follicular-lymphomas
#4
Akiko Miyagi Maeshima, Hirokazu Taniguchi, Tomotaka Suzuki, Sayako Yuda, Kosuke Toyoda, Nobuhiko Yamauchi, Shinichi Makita, Suguru Fukuhara, Wataru Munakata, Dai Maruyama, Yukio Kobayashi, Yutaka Saito, Kensei Tobinai
We compared the incidence, esophagogastroduodenoscopy (EGD) findings, and histopathologic characteristics of gastric and duodenal follicular lymphomas (FL). Of 626 FL cases, primary gastric FL and secondary gastric involvement of FL were observed in 1% and 5% of the cases, respectively, which were lower incidences than duodenal FL (10% and 9%, respectively). Gastric FL usually appeared as submucosal tumors (primary, 71%: secondary, 79%), whereas duodenal FL as granular lesions (primary, 92%: secondary, 87%)...
May 10, 2017: Human Pathology
https://www.readbyqxmd.com/read/28498098/germinal-center-b-cell-development-has-distinctly-regulated-stages-completed-by-disengagement-from-t-cell-help
#5
Ting-Ting Zhang, David G Gonzalez, Christine M Cote, Steven M Kerfoot, Shaoli Deng, Yuqing Cheng, Masaki Magari, Ann M Haberman
To reconcile conflicting reports on the role of CD40 signaling in germinal center (GC) formation, we examined the earliest stages of murine GC B cell differentiation. Peri-follicular GC precursors first expressed intermediate levels of BCL6 while co-expressing the transcription factors RelB and IRF4, the latter known to repress Bcl6 transcription. Transition of GC precursors to the BCL6(hi) follicular state was associated with cell division, although the number of required cell divisions was immunogen dose dependent...
May 12, 2017: ELife
https://www.readbyqxmd.com/read/28496444/the-transcription-factor-c-maf-promotes-the-differentiation-of-follicular-helper-t-cells
#6
Fabienne Andris, Sébastien Denanglaire, Maelle Anciaux, Mélanie Hercor, Hind Hussein, Oberdan Leo
Follicular helper T cells (Tfh) have been identified as the primary cell subpopulation regulating B cell responses in germinal centers, thus supporting high-affinity antibody production. Among the transcription factors orchestrating Tfh cell differentiation and function, the role played by the proto-oncogene c-Maf remains poorly characterized. We report herein that selective loss of c-Maf expression in the T cell compartment results in defective development of Tfh cells in response to both antigen/adjuvant vaccinations and commensal intestinal bacteria...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28487787/ebv-negative-monomorphic-b-cell-posttransplant-lymphoproliferative-disorder-with-marked-morphologic-pleomorphism-and-pathogenic-mutations-in-asxl1-bcor-cdkn2a-nf1-and-tp53
#7
Agata M Bogusz
Posttransplant lymphoproliferative disorders (PTLDs) are a diverse group of lymphoid or plasmacytic proliferations frequently driven by Epstein-Barr virus (EBV). EBV-negative PTLDs appear to represent a distinct entity. This report describes an unusual case of a 33-year-old woman that developed a monomorphic EBV-negative PTLD consistent with diffuse large B-cell lymphoma (DLBCL) 13 years after heart-lung transplant. Histological examination revealed marked pleomorphism of the malignant cells including nodular areas reminiscent of classical Hodgkin lymphoma (cHL) with abundant large, bizarre Hodgkin-like cells...
2017: Case Reports in Hematology
https://www.readbyqxmd.com/read/28487311/egr2-and-3-control-adaptive-immune-responses-by-temporally-uncoupling-expansion-from-t-cell-differentiation
#8
Tizong Miao, Alistair L J Symonds, Randeep Singh, Janine D Symonds, Ane Ogbe, Becky Omodho, Bo Zhu, Suling Li, Ping Wang
Egr2 and 3 are important for maintaining immune homeostasis. Here we define a fundamental function of Egr2 and 3 operating as a checkpoint that controls the transition between clonal expansion and differentiation of effector T cells. Egr2 and 3 deficiency resulted in defective clonal expansion but hyperactivation and excessive differentiation of T cells in response to viral infection. Conversely, sustained Egr2 expression enhanced expansion but severely impaired effector differentiation. Egr2 bound to and controlled the expression of genes regulating proliferation (Myc and Myb) and differentiation repressors (Bcl6, Id3), while repressing transcription factors required for effector function (Zeb2, RORa, RORc, and Bhlhe40)...
May 9, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28485934/discovery-of-pyrazolo-1-5-a-pyrimidine-b-cell-lymphoma-6-bcl6-binders-and-optimization-to-high-affinity-macrocyclic-inhibitors
#9
William McCoull, Roman D Abrams, Erica Anderson, Kevin Blades, Peter Barton, Matthew Box, Jonathan Burgess, Kate Byth, Qing Cao, Claudio Chuaqui, Rodrigo J Carbajo, Tony Cheung, Erin Code, Andrew D Ferguson, Shaun Fillery, Nathan O Fuller, Eric Gangl, Ning Gao, Matthew Grist, David Hargreaves, Martin R Howard, Jun Hu, Paul D Kemmitt, Jennifer E Nelson, Nichole O'Connell, D Bryan Prince, Piotr Raubo, Philip B Rawlins, Graeme R Robb, Junjie Shi, Michael J Waring, David Whittaker, Marta Wylot, Xiahui Zhu
Inhibition of the protein-protein interaction between B-cell lymphoma 6 (BCL6) and corepressors has been implicated as a therapeutic target in diffuse large B-cell lymphoma (DLBCL) cancers and profiling of potent and selective BCL6 inhibitors are critical to test this hypothesis. We identified a pyrazolo[1,5-a]pyrimidine series of BCL6 binders from a fragment screen in parallel with a virtual screen. Using structure-based drug design, binding affinity was increased 100000-fold. This involved displacing crystallographic water, forming new ligand-protein interactions and a macrocyclization to favor the bioactive conformation of the ligands...
May 9, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28484447/hiv-1-and-siv-predominantly-use-ccr5-expressed-on-a-precursor-population-to-establish-infection-in-t-follicular-helper-cells
#10
Yin Xu, Chansavath Phetsouphanh, Kazuo Suzuki, Anu Aggrawal, Stephanie Graff-Dubois, Michael Roche, Michelle Bailey, Sheilajen Alcantara, Kieran Cashin, Rahuram Sivasubramaniam, Kersten K Koelsch, Brigitte Autran, Richard Harvey, Paul R Gorry, Arnaud Moris, David A Cooper, Stuart Turville, Stephen J Kent, Anthony D Kelleher, John Zaunders
BACKGROUND: T follicular helper (Tfh) cells are increasingly recognized as a major reservoir of HIV infection that will likely need to be addressed in approaches to curing HIV. However, Tfh express minimal CCR5, the major coreceptor for HIV-1, and the mechanism by which they are infected is unclear. We have previously shown that macaque Tfh lack CCR5, but are infected in vivo with CCR5-using SIV at levels comparable to other memory CD4(+) T cells. Similarly, human splenic Tfh cells are highly infected with HIV-1 DNA...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28484026/correction-for-xu-et-al-bcl6-promotes-glioma-and-serves-as-a-therapeutic-target
#11
(no author information available yet)
No abstract text is available yet for this article.
May 8, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28472619/toll-like-receptor-4-and-hepatocellular-carcinoma-a-systematic-review
#12
REVIEW
Zahra Sepehri, Zohre Kiani, Farhad Kohan, Seyed Moayed Alavian, Saeid Ghavami
INTRODUCTION: Toll like receptor 4 (TLR4) is an extracellular pathogen recognition receptor (PRR) which recognizes a wide range of pathogens and damage associated molecular patterns (PAMPs and DAMPs). It can activate intracellular signaling and consequently transcription factors which participate in transcription from either immune related or malignancy genes. Thus, it has been hypothesized that TLR4 may be a cause of hepatocellular carcinoma (HCC). This article has reviewed the roles of TLR4 in the pathogenesis of HCC...
May 1, 2017: Life Sciences
https://www.readbyqxmd.com/read/28471657/discovery-of-a-b-cell-lymphoma-6-protein-protein-interaction-inhibitor-by-a-biophysics-driven-fragment-based-approach
#13
Yusuke Kamada, Nozomu Sakai, Satoshi Sogabe, Koh Ida, Hideyuki Oki, Kotaro Sakamoto, Weston Lane, Gyorgy Snell, Motoo Iida, Yasuhiro Imaeda, Junichi Sakamoto, Junji Matsui
B-cell lymphoma 6 (BCL6) is a transcriptional factor that expresses in lymphocytes and regulates the differentiation and proliferation of lymphocytes. Therefore, BCL6 is a therapeutic target for autoimmune diseases and cancer treatment. This report presents the discovery of BCL6-corepressor interaction inhibitors by using a biophysics-driven fragment-based approach. Using the surface plasmon resonance (SPR)-based fragment screening, we successfully identified fragment 1 (SPR KD = 1200 μM, ligand efficiency (LE) = 0...
May 11, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28440396/downregulation-of-mir-10b-promotes-osteoblast-differentiation-through-targeting-bcl6
#14
Jizhou Yang, Shaojie Wang, Fengxian Wang, Xiaohong Mu, Yi Qu, Ziyi Zhao, Xing Yu
MicroRNAs (miRNAs or miRs) have been shown to play a critical role in osteoblast differentiation. miR-10b has been found to be downregulated during osteoblast differentiation; however, its precise effect on osteoblast differentiation remains unknown. In this study, we aimed to investigate the potential role of miR-10b and the potential underlying mechanism in regulating osteoblast differentiation. We found that miR-10b was downregulated during osteoblast differentiation. Overexpression of miR-10b inhibited osteoblast differentiation, whereas the suppression of miR-10b promoted osteoblast differentiation...
April 20, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28428203/tslp-activated-dendritic-cells-induce-human-t-follicular-helper-cell-differentiation-through-ox40-ligand
#15
Lucia Pattarini, Coline Trichot, Sofia Bogiatzi, Maximilien Grandclaudon, Stephan Meller, Zela Keuylian, Melanie Durand, Elisabetta Volpe, Stefania Madonna, Andrea Cavani, Andrea Chiricozzi, Marco Romanelli, Toshiyuki Hori, Alain Hovnanian, Bernhard Homey, Vassili Soumelis
T follicular helper cells (Tfh) are important regulators of humoral responses. Human Tfh polarization pathways have been thus far associated with Th1 and Th17 polarization pathways. How human Tfh cells differentiate in Th2-skewed environments is unknown. We show that thymic stromal lymphopoietin (TSLP)-activated dendritic cells (DCs) promote human Tfh differentiation from naive CD4 T cells. We identified a novel population, distinct from Th2 cells, expressing IL-21 and TNF, suggestive of inflammatory cells...
May 1, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28420429/deptor-maintains-plasma-cell-differentiation-and-favorably-affects-prognosis-in-multiple-myeloma
#16
Dalia Quwaider, Luis A Corchete, Irena Misiewicz-Krzeminska, María E Sarasquete, José J Pérez, Patryk Krzeminski, Noemí Puig, María Victoria Mateos, Ramón García-Sanz, Ana B Herrero, Norma C Gutiérrez
BACKGROUND: The B cell maturation process involves multiple steps, which are controlled by relevant pathways and transcription factors. The understanding of the final stages of plasma cell (PC) differentiation could provide new insights for therapeutic strategies in multiple myeloma (MM). Here, we explore the role of DEPTOR, an mTOR inhibitor, in the terminal differentiation of myeloma cells, and its potential impact on patient survival. METHODS: The expression level of DEPTOR in MM cell lines and B cell populations was measured by real-time RT-PCR, and/or Western blot analysis...
April 18, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28377453/combination-therapy-targeting-bcl6-and-phospho-stat3-defeats-intra-tumor-heterogeneity-in-a-subset-of-non-small-cell-lung-cancers
#17
Dhruba Deb, Satwik Rajaram, Jill E Larsen, Patrick P Dospoy, Rossella Marullo, Long-Shan Li, Kimberley Avila, Leandro Cerchietti, Fengtian Xue, John Minna, Steven J Altschuler, Lani F Wu
Oncogene-specific changes in cellular signaling have been widely observed in lung cancer. Here, we investigated how these alterations could affect signaling heterogeneity and suggest novel therapeutic strategies. We compared signaling changes across six human bronchial epithelial cell (HBEC) strains that were systematically transformed with various combinations of TP53, K-RAS, and MYC-oncogenic alterations commonly found in non-small cell lung cancer (NSCLC). We interrogated at single-cell resolution how these alterations could affect classic readouts (β-CATENIN, SMAD2/3, phospho-STAT3, P65, FOXO1 and phospho-ERK1/2) of key pathways commonly affected in NSCLC...
April 4, 2017: Cancer Research
https://www.readbyqxmd.com/read/28368400/interferon-%C3%AE-is-a-stat1-dependent-direct-inducer-of-bcl6-expression-in-imatinib-treated-chronic-myeloid-leukemia-cells
#18
H S Madapura, N Nagy, D Ujvari, T Kallas, M C L Kröhnke, S Amu, M Björkholm, L Stenke, P K Mandal, J S McMurray, M Keszei, L S Westerberg, H Cheng, F Xue, G Klein, E Klein, D Salamon
B-cell CLL/lymphoma 6 (BCL6) exerts oncogenic effects in several human hematopoietic malignancies including chronic myeloid leukemia (CML), where BCL6 expression was shown to be essential for CML stem cell survival and self-renewal during imatinib mesylate (IM) treatment. As several lines of evidence suggest that interferon γ (IFNγ) production in CML patients might have a central role in the response to tyrosine kinase inhibitor (TKI) therapy, we analyzed if IFNγ modulates BCL6 expression in CML cells. Although separate IFNγ or IM treatment only slightly upregulated BCL6 expression, combined treatment induced remarkable BCL6 upregulation in CML lines and primary human CD34+ CML stem cells...
April 3, 2017: Oncogene
https://www.readbyqxmd.com/read/28368397/molecular-impact-of-selective-nfkb1-and-nfkb2-signaling-on-dlbcl-phenotype
#19
X Guo, J L Koff, A B Moffitt, M Cinar, S Ramachandiran, Z Chen, J M Switchenko, M Mosunjac, S G Neill, K P Mann, M Bagirov, Y Du, Y Natkunam, H J Khoury, M R Rossi, W Harris, C R Flowers, I S Lossos, L H Boise, S S Dave, J Kowalski, L Bernal-Mizrachi
Diffuse large B-cell lymphoma (DLBCL) has been categorized into two molecular subtypes that have prognostic significance, namely germinal center B-cell like (GCB) and activated B-cell like (ABC). Although ABC-DLBCL has been associated with NF-κB activation, the relationships between activation of specific NF-κB signals and DLBCL phenotype remain unclear. Application of novel gene expression classifiers identified two new DLBCL categories characterized by selective p100 (NF-κB2) and p105 (NF-κB1) signaling...
April 3, 2017: Oncogene
https://www.readbyqxmd.com/read/28363935/poz-at-hook-and-zinc-finger-containing-protein-patz-interacts-with-the-human-oncogene-b-cell-lymphoma-6-bcl6-and-is-required-for-its-negative-autoregulation
#20
Raffaela Pero, Dario Palmieri, Tiziana Angrisano, Teresa Valentino, Antonella Federico, Renato Franco, Francesca Lembo, Andres J Klein-Szanto, Luigi Del Vecchio, Donatella Montanaro, Simona Keller, Claudio Arra, Vasiliki Papadopoulou, Simon D Wagner, Carlo M Croce, Alfredo Fusco, Lorenzo Chiariotti, Monica Fedele
No abstract text is available yet for this article.
March 31, 2017: Journal of Biological Chemistry
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