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https://www.readbyqxmd.com/read/28208987/bcl6-mrna-expression-level-in-invasive-duct-carcinoma-not-otherwise-specified
#1
Eman Badr, Eman Masoud, Asmaa Gaber Abdou, Marwa Serag Eldien
INTRODUCTION: B-Cell Lymphoma 6 (BCL6) has an oncogenic role in tumourigenesis of various malignancies. It represses genes involved in terminal differentiation and plays complementary role with Signal Transducer and Activator of Transcription 3 (STAT3) in triple-negative breast cancer cellular function. AIM: To evaluate the expression of BCL6 in cancer breast and determine its correlation with the clinico-pathological features including the molecular subtype of breast carcinoma...
December 2016: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28150777/pathologically-expanded-peripheral-t-helper-cell-subset-drives-b-cells-in-rheumatoid-arthritis
#2
Deepak A Rao, Michael F Gurish, Jennifer L Marshall, Kamil Slowikowski, Chamith Y Fonseka, Yanyan Liu, Laura T Donlin, Lauren A Henderson, Kevin Wei, Fumitaka Mizoguchi, Nikola C Teslovich, Michael E Weinblatt, Elena M Massarotti, Jonathan S Coblyn, Simon M Helfgott, Yvonne C Lee, Derrick J Todd, Vivian P Bykerk, Susan M Goodman, Alessandra B Pernis, Lionel B Ivashkiv, Elizabeth W Karlson, Peter A Nigrovic, Andrew Filer, Christopher D Buckley, James A Lederer, Soumya Raychaudhuri, Michael B Brenner
CD4(+) T cells are central mediators of autoimmune pathology; however, defining their key effector functions in specific autoimmune diseases remains challenging. Pathogenic CD4(+) T cells within affected tissues may be identified by expression of markers of recent activation. Here we use mass cytometry to analyse activated T cells in joint tissue from patients with rheumatoid arthritis, a chronic immune-mediated arthritis that affects up to 1% of the population. This approach revealed a markedly expanded population of PD-1(hi)CXCR5(-)CD4(+) T cells in synovium of patients with rheumatoid arthritis...
1, 2017: Nature
https://www.readbyqxmd.com/read/28143955/the-eph-related-tyrosine-kinase-ligand-ephrin-b1-marks-germinal-center-and-memory-precursor-b-cells
#3
Brian J Laidlaw, Timothy H Schmidt, Jesse A Green, Christopher D C Allen, Takaharu Okada, Jason G Cyster
Identification of germinal center (GC) B cells is typically reliant on the use of surface activation markers that exhibit a wide range of expression. Here, we identify Ephrin-B1, a ligand for Eph-related receptor tyrosine kinases, as a specific marker of mature GC B cells. The number of Ephrin-B1(+) GC B cells increases during the course of an immune response with Ephrin-B1(+) GC B cells displaying elevated levels of Bcl6, S1pr2, and Aicda relative to their Ephrin-B1(-) counterparts. We further identified a small proportion of recently dividing, somatically mutated Ephrin-B1(+) GC B cells that have begun to down-regulate Bcl6 and S1pr2 and express markers associated with memory B cells, such as CD38 and EBI2...
January 31, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28106131/hif-1%C3%AE-induction-during-reperfusion-avoids-maladaptive-repair-after-renal-ischemia-reperfusion-involving-mir127-3p
#4
Elisa Conde, Sara Giménez-Moyano, Laura Martín-Gómez, Macarena Rodríguez, M Edurne Ramos, Elia Aguado-Fraile, Ignacio Blanco-Sanchez, Ana Saiz, María Laura García-Bermejo
Ischemia/reperfusion (I/R) leads to Acute Kidney Injury. HIF-1α is a key factor during organ response to I/R. We previously demonstrated that HIF-1α is induced during renal reperfusion, after ischemia. Here we investigate the role of HIF-1α and the HIF-1α dependent mechanisms in renal repair after ischemia. By interference of HIF-1α in a rat model of renal I/R, we observed loss of expression and mis-localization of e-cadherin and induction of α-SMA, MMP-13, TGFβ, and collagen I. Moreover, we demonstrate that HIF-1α inhibition promotes renal cell infiltrates by inducing IL-1β, TNF-α, MCP-1 and VCAM-1, through NFkB activity...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28096407/development-of-chronic-allergic-responses-by-dampening-bcl6-mediated-suppressor-activity-in-memory-t-helper-2-cells
#5
Takashi Ogasawara, Masahiko Hatano, Hisae Satake, Jun Ikari, Toshibumi Taniguchi, Nobuhide Tsuruoka, Haruko Watanabe-Takano, Lisa Fujimura, Akemi Sakamoto, Hirokuni Hirata, Kumiya Sugiyama, Yasutsugu Fukushima, Susumu Nakae, Kenji Matsumoto, Hirohisa Saito, Takeshi Fukuda, Kazuhiro Kurasawa, Koichiro Tatsumi, Takeshi Tokuhisa, Masafumi Arima
Mice deficient in the transcriptional repressor B-cell CLL/lymphoma 6 (Bcl6) exhibit similar T helper 2 (TH2) immune responses as patients with allergic diseases. However, the molecular mechanisms underlying Bcl6-directed regulation of TH2 cytokine genes remain unclear. We identified multiple Bcl6/STAT binding sites (BSs) in TH2 cytokine gene loci. We found that Bcl6 is modestly associated with the BSs, and it had no significant effect on cytokine production in newly differentiated TH2 cells. Contrarily, in memory TH2 (mTH2) cells derived from adaptively transferred TH2 effectors, Bcl6 outcompeted STAT5 for binding to TH2 cytokine gene loci, particularly Interleukin4 (Il4) loci, and attenuated GATA binding protein 3 (GATA3) binding to highly conserved intron enhancer regions in mTH2 cells...
January 31, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28065665/unbiased-identification-of-blood-based-biomarkers-for-pulmonary-tuberculosis-by-modeling-and-mining-molecular-interaction-networks
#6
Awanti Sambarey, Abhinandan Devaprasad, Abhilash Mohan, Asma Ahmed, Soumya Nayak, Soumya Swaminathan, George D'Souza, Anto Jesuraj, Chirag Dhar, Subash Babu, Annapurna Vyakarnam, Nagasuma Chandra
Efficient diagnosis of tuberculosis (TB) is met with multiple challenges, calling for a shift of focus from pathogen-centric diagnostics towards identification of host-based multi-marker signatures. Transcriptomics offer a list of differentially expressed genes, but cannot by itself identify the most influential contributors to the disease phenotype. Here, we describe a computational pipeline that adopts an unbiased approach to identify a biomarker signature. Data from RNA sequencing from whole blood samples of TB patients were integrated with a curated genome-wide molecular interaction network, from which we obtain a comprehensive perspective of variations that occur in the host due to TB...
February 2017: EBioMedicine
https://www.readbyqxmd.com/read/28062671/targeting-hdac3-in-crebbp-mutant-lymphomas-counterstrikes-unopposed-enhancer-deacetylation-of-b-cell-signaling-and-immune-response-genes
#7
Uta E Höpken
The cellular phenotype of B-cell lymphomas arising from B cells undergoing germinal center reactions, such as follicular lymphoma and diffuse large B-cell lymphoma, is strongly shaped by mutations in chromatin-modifying genes. The work presented by Jiang and colleagues addresses how somatic mutations in CREBBP disable acetylation and cause unopposed deacetylation by BCL6/SMRT/HDAC3 complexes on enhancers of B-cell signaling and immune response genes. This opens a therapeutic avenue toward targeted inhibition of CREBBP-mutant lymphomas by HDAC inhibitors...
January 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28061782/double-hit-lymphomas-clinical-morphological-immunohistochemical-and-cytogenetic-study-in-a-series-of-brazilian-patients-with-high-grade-non-hodgkin-lymphoma
#8
Cristiano Claudino Oliveira, Helena Maciel-Guerra, Luan Kucko, Eric Jun Hirama, Américo Delgado Brilhante, Francisco Carlos Quevedo, Isabela Werneck da Cunha, Fernando Augusto Soares, Ligia Niero-Melo, Patrícia Pintor Dos Reis, Maria Aparecida Custodio Domingues
BACKGROUND: Double-hit lymphomas (DHL) are rare high-grade neoplasms characterized by two translocations: one involving the gene MYC and another involving genes BCL2 or BCL6, whose diagnosis depends on cytogenetic examination. This research studied DHL and morphological and/or immunophenotypic factors associated with the detection of these translocations in a group of high-grade non-Hodgkin lymphoma cases. METHOD: Clinical and morphological reviews of 120 cases diagnosed with diffuse large B-cell lymphoma and Burkitt lymphoma were conducted...
January 7, 2017: Diagnostic Pathology
https://www.readbyqxmd.com/read/28039906/prognostic-impact-of-cd5-expression-in-diffuse-large-b-cell-lymphoma-in-patients-treated-with-rituximab-epoch
#9
Beenu Thakral, L Jeffrey Medeiros, Parth Desai, Pei Lin, C Cameron Yin, Guilin Tang, Joseph D Khoury, Shimin Hu, Jie Xu, Sanam Loghavi, Bei Hu, Yasuhiro Oki, Shaoying Li
OBJECTIVES: CD5-positive (CD5+) diffuse large B-cell lymphoma (DLBCL) represents 5%-10% of all DLBCL cases, which has been associated with a poorer prognosis in patients treated with R-CHOP. Prognostic impact of CD5 expression in patients with DLBCL treated with R-EPOCH has not been evaluated. METHODS: We studied 130 patients with de novo DLBCL who received frontline R-EPOCH therapy. The clinicopathologic features and overall survival (OS) were compared between patients with CD5+ and CD5- DLBCL...
December 31, 2016: European Journal of Haematology
https://www.readbyqxmd.com/read/28038709/signet-ring-cell-lymphoma-clinicopathologic-immunohistochemical-and-fluorescence-in-situ-hybridization-studies-of-7-cases
#10
Shanxiang Zhang, Jihong Sun, Yanan Fang, Mehdi Nassiri, Lanting Liu, Jiehao Zhou, Ryan Stohler, Haki Choi, Gail H Vance
CONTEXT: Signet-ring cell lymphoma (SRCL) is a rare morphologic variant of non-Hodgkin lymphoma. Although it was initially reported as a rare morphologic variant of follicular lymphoma (FL), SRCL has to date been described in most types of non-Hodgkin lymphoma, mostly as single-case reports. OBJECTIVE: To study SRCL systematically by immunohistochemical stains and fluorescent in situ hybridization analyses. DESIGN: Seven SRCL cases were stained for CD3, CD5, CD20, PAX-5, CD10, CD21, CD23, cyclin D1, BCL2, BCL6, Ki-67, and MUM-1, and were analyzed by fluorescent in situ hybridization for BCL2, BCL6, MYC, and MALT1 rearrangements...
February 2017: Annals of Diagnostic Pathology
https://www.readbyqxmd.com/read/28034071/relapsed-or-refractory-double-expressor-and-double-hit-lymphomas-have-inferior-progression-free-survival-after-autologous-stem-cell-transplantation
#11
Alex F Herrera, Matthew Mei, Lawrence Low, Haesook T Kim, Gabriel K Griffin, Joo Y Song, Reid W Merryman, Victoria Bedell, Christine Pak, Heather Sun, Tanya Paris, Tracey Stiller, Jennifer R Brown, Lihua E Budde, Wing C Chan, Robert Chen, Matthew S Davids, Arnold S Freedman, David C Fisher, Eric D Jacobsen, Caron A Jacobson, Ann S LaCasce, Joyce Murata-Collins, Auayporn P Nademanee, Joycelynne M Palmer, German A Pihan, Raju Pillai, Leslie Popplewell, Tanya Siddiqi, Aliyah R Sohani, Jasmine Zain, Steven T Rosen, Larry W Kwak, David M Weinstock, Stephen J Forman, Dennis D Weisenburger, Young Kim, Scott J Rodig, Amrita Krishnan, Philippe Armand
Purpose Double-hit lymphomas (DHLs) and double-expressor lymphomas (DELs) are subtypes of diffuse large B-cell lymphoma (DLBCL) associated with poor outcomes after standard chemoimmunotherapy. Data are limited regarding outcomes of patients with relapsed or refractory (rel/ref) DEL or DHL who undergo autologous stem-cell transplantation (ASCT). We retrospectively studied the prognostic impact of DEL and DHL status on ASCT outcomes in patients with rel/ref DLBCL. Methods Patients with chemotherapy-sensitive rel/ref DLBCL who underwent ASCT at two institutions and in whom archival tumor material was available were enrolled...
January 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28031181/ibrutinib-inhibits-pre-bcr-b-cell-acute-lymphoblastic-leukemia-progression-by-targeting-btk-and-blk
#12
Ekaterina Kim, Christian Hurtz, Stefan Koehrer, Zhiqiang Wang, Sriram Balasubramanian, Betty Y Chang, Markus Müschen, R Eric Davis, Jan A Burger
Targeting B cell receptor (BCR) signaling is a successful therapeutic strategy in mature B cell malignancies. Precursor BCR (pre-BCR) signaling, which is critical during normal B lymphopoiesis, also plays an important role in pre-BCR(+) B cell acute lymphoblastic leukemia (B-ALL). Here, we investigated the activity and mechanism of action of the BTK inhibitor ibrutinib in preclinical models of B-ALL. Pre-BCR(+) ALL cells were exquisitely sensitive to ibrutinib at therapeutically relevant drug concentrations...
December 28, 2016: Blood
https://www.readbyqxmd.com/read/28030830/ikaros-regulation-of-the-bcl6-bach2-axis-and-its-clinical-relevance-in-acute-lymphoblastic-leukemia
#13
Zheng Ge, Xilian Zhou, Yan Gu, Qi Han, Jianyong Li, Baoan Chen, Qinyu Ge, Elanora Dovat, Jonathon L Payne, Tianyu Sun, Chunhua Song, Sinisa Dovat
B-Cell CLL/Lymphoma 6 (BCL6) is a proto-oncogene that is highly expressed in acute lymphoblastic leukemia (ALL). BTB and CNC Homology 1 Basic Leucine Zipper Transcription Factor 2 (BACH2) is a suppressor of transcription. The BACH2-BCL6 balance controls selection at the pre-B cell receptor checkpoint by regulating p53 expression. However, the underlying mechanism and the clinical relevance of the BCL6/BACH2 axis are unknown. Here, we found that Ikaros, a tumor suppressor encoded by IKZF1, directly binds to both the BCL6 and BACH2 promoters where it suppresses BCL6 and promotes BACH2 expression in B-cell ALL (B-ALL) cells...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28024482/-effects-of-homoharringtonine-combined-with-imatinib-on-k562-cell-apoptosis-and-bcl6-expression
#14
Qian Wang, Wei Ding, Jing-Jing Wu, Yi-Han Ding, Yu-Feng Li
OBJECTIVE: To explore the effects of homoharringtonine (HHT) alone or combined with imatinib (IM) on K562 cell proliferation and apoptosis, as well as the mRNA and protein expression of BCL6. METHODS: The CCK-8 was used to detect the inhibitory effect of drugs on cell growth, the flow cytometry was used to detect the cell apoptosis. The expression of BCL6 protein was assayed by Western blot, and BCL6 mRNA expression was detected by RT-PCR. RESULTS: HHT alone displayed a proliferation inhibition effect with dose- dependent manner, and induced apotosis; after combination of HHT and IM drugs, both the inhibitory rate and the apoptosis rate were significantly increased compared with the drug alone(P<0...
December 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28018990/the-tcf1-bcl6-axis-counteracts-type-i-interferon-to-repress-exhaustion-and-maintain-t-cell-stemness
#15
Tuoqi Wu, Yun Ji, E Ashley Moseman, Haifeng C Xu, Monica Manglani, Martha Kirby, Stacie M Anderson, Robin Handon, Elizabeth Kenyon, Abdel Elkahloun, Weiwei Wu, Philipp A Lang, Luca Gattinoni, Dorian B McGavern, Pamela L Schwartzberg
During chronic viral infections and in cancer, T cells become dysfunctional, a state known as T cell exhaustion. Although it is well recognized that memory CD8 T cells account for the persistence of CD8 T cell immunity after acute infection, how exhausted T cells persist remains less clear. Using chronic infection with lymphocytic choriomeningitis virus clone 13 and tumor samples, we demonstrate that CD8 T cells differentiate into a less exhausted TCF1(high) and a more exhausted TCF1(low) population. Virus-specific TCF1(high) CD8 T cells, which resemble T follicular helper (TFH) cells, persist and recall better than do TCF1(low) cells and act as progenitor cells to replenish TCF1(low) cells...
December 23, 2016: Science Immunology
https://www.readbyqxmd.com/read/27993575/b-cell-post-transplant-lymphoproliferative-disorder-isolated-to-the-central-nervous-system-is-ebv-positive-and-lacks-p53-and-myc-expression-by-immunohistochemistry
#16
Andrew Sundin, Bartosz J Grzywacz, Sophia Yohe, Michael A Linden, Elizabeth L Courville
In this retrospective study from one institution, we performed a clinicopathologic study of a cohort of patients with post-transplant lymphoproliferative disorder (PTLD) confined to the central nervous system. We also identified a comparison cohort of patients with de novo primary diffuse large B-cell lymphoma of the central nervous system. We performed a detailed morphologic review, evaluated Epstein-Barr Virus (EBV) by in-situ hybridization, and interpreted a panel of immunohistochemical stains in a subset of cases including Hans classification markers (CD10, BCL6, MUM1), p53, CD30, myc, and BCL2...
December 16, 2016: Human Pathology
https://www.readbyqxmd.com/read/27966264/pd1-and-pdl1-expression-in-primary-central-nervous-system-diffuse-large-b-cell-lymphoma-are-frequent-and-expression-of-pd1-predicts-poor-survival
#17
Marion Four, Valère Cacheux, Ariane Tempier, Dolorès Platero, Michel Fabbro, Grégory Marin, Nicolas Leventoux, Valérie Rigau, Valérie Costes-Martineau, Vanessa Szablewski
Primary central nervous system diffuse large B-cell lymphoma (PCNS-DLBCL) is a rare and aggressive type of diffuse large B-cell lymphoma (DLBCL) whit poorly understood pathogenesis. Finding biomarkers associated with patient survival may be important for understanding its physiopathology and to develop new therapeutic approaches. We investigated 32 PCNS-DLBCL from immunocompetent patients for BCL2, CMYC, LMO2, and P53 expression and for cytogenetic aberrations of BCL2, BCL6, and MYC genes, all known for their prognostic value in systemic DLBCL (s-DLBCL)...
December 13, 2016: Hematological Oncology
https://www.readbyqxmd.com/read/27921272/bcl6-locus-is-hypermethylated-in-angioimmunoblastic-t-cell-lymphoma
#18
Shoko Nishizawa, Mamiko Sakata-Yanagimoto, Keiichiro Hattori, Hideharu Muto, Tran Nguyen, Koji Izutsu, Kenichi Yoshida, Seishi Ogawa, Naoya Nakamura, Shigeru Chiba
BCL6, a master transcription factor for differentiation of follicular helper T (TFH) cells, is highly expressed in angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphomas (PTCL) containing tumor cells with TFH features. TET2, encoding an epigenetic regulator, is frequently mutated in AITL/PTCL. We previously reported that Tet2 knockdown mice developed T-cell lymphomas with TFH features. Hypermethylation of the Bcl6 locus followed by BCL6 upregulation was thought to be the key event for lymphoma development in mice...
December 5, 2016: International Journal of Hematology
https://www.readbyqxmd.com/read/27907212/diffuse-large-b-cell-lymphoma-cell-line-u-2946-model-for-mcl1-inhibitor-testing
#19
Hilmar Quentmeier, Hans G Drexler, Vivien Hauer, Roderick A F MacLeod, Claudia Pommerenke, Cord C Uphoff, Margarete Zaborski, Mattias Berglund, Gunilla Enblad, Rose-Marie Amini
Diffuse large B cell lymphoma (DLBCL) is the most common form of non-Hodgkin lymphoma worldwide. We describe the establishment and molecular characteristics of the DLBCL cell line U-2946. This cell line was derived from a 52-year-old male with DLBCL. U-2946 cells carried the chromosomal translocation t(8;14) and strongly expressed MYC, but not the mature B-cell lymphoma associated oncogenes BCL2 and BCL6. Instead, U-2946 cells expressed the antiapoptotic BCL2 family member MCL1 which was highly amplified genomically (14n)...
2016: PloS One
https://www.readbyqxmd.com/read/27899526/dynamic-pre-bcr-homodimers-fine-tune-autonomous-survival-signals-in-b-cell-precursor-acute-lymphoblastic-leukemia
#20
M Frank Erasmus, Ksenia Matlawska-Wasowska, Ichiko Kinjyo, Avanika Mahajan, Stuart S Winter, Li Xu, Michael Horowitz, Diane S Lidke, Bridget S Wilson
The pre-B cell receptor (pre-BCR) is an immature form of the BCR critical for early B lymphocyte development. It is composed of the membrane-bound immunoglobulin (Ig) heavy chain, surrogate light chain components, and the signaling subunits Igα and Igβ. We developed monovalent quantum dot (QD)-labeled probes specific for Igβ to study the behavior of pre-BCRs engaged in autonomous, ligand-independent signaling in live B cells. Single-particle tracking revealed that QD-labeled pre-BCRs engaged in transient, but frequent, homotypic interactions...
November 29, 2016: Science Signaling
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