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https://www.readbyqxmd.com/read/27907212/diffuse-large-b-cell-lymphoma-cell-line-u-2946-model-for-mcl1-inhibitor-testing
#1
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
#2
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
https://www.readbyqxmd.com/read/27898346/amp-kinase-promotes-bcl6-expression-in-both-mouse-and-human-t-cells
#3
Markus M Xie, Tohti Amet, Hong Liu, Qigui Yu, Alexander L Dent
The transcription factor Bcl6 is a master regulator of follicular helper T (TFH) cells, and understanding the signaling pathway that induces Bcl6 and TFH cell differentiation is therefore critical. IL-2 produced during T cell activation inhibits Bcl6 expression but how TFH cells evade IL-2 inhibition is not completely understood. Here we show that Bcl6 is highly up-regulated in activated CD4 T cells following glucose deprivation (GD), and this pathway is insensitive to inhibition by IL-2. Similar to GD, the glucose analog 2-deoxyglucose (2DG) inhibits glycolysis, and 2DG induced Bcl6 expression in activated CD4 T cells...
November 26, 2016: Molecular Immunology
https://www.readbyqxmd.com/read/27888664/ebv-associated-but-hhv8-unrelated-double-hit-effusion-based-lymphoma
#4
Bo-Jung Chen, David Yen-Ting Chen, Chun-Chi Kuo, Shih-Sung Chuang
Effusion-based lymphoma is a rare and unique type of large B-cell lymphoma presenting in effusion without a mass lesion. It shares many clinicopathological features with primary effusion lymphoma (PEL), but is distinct from PEL by the absence of HHV8 association. Double hit lymphoma (DHL) is an aggressive B-cell lymphoma, defined by concurrent rearrangement of MYC and BCL2 or BCL6. DHL often presents as lymphadenopathy or an extranodal mass, but rarely occurs in effusion. Here we report a 61-year-old male with alcoholic cirrhosis presenting as massive ascites and left pleural effusion...
November 26, 2016: Diagnostic Cytopathology
https://www.readbyqxmd.com/read/27881582/the-expanding-role-of-the-bcl6-oncoprotein-as-a-cancer-therapeutic-target
#5
Mariano G Cardenas, Erin Oswald, Wenbo Yu, Fengtian Xue, Alexander D MacKerell, Ari M Melnick
BCL6 was initially discovered as an oncogene in B-cell lymphomas, where it drives the malignant phenotype by repressing proliferation and DNA damage checkpoints and blocking B-cell terminal differentiation. BCL6 mediates its effects by binding to hundreds of target genes, and then repressing these genes by recruiting several different chromatin modifying corepressor complexes. Structural characterization of BCL6-corepressor complexes suggested that BCL6 might be a druggable target. Accordingly a number of compounds have been designed to bind to BCL6 and block corepressor recruitment...
November 23, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27867103/lymphoblastic-lymphoma-with-a-triple-hit-profile-a-rare-but-distinct-and-relevant-entity
#6
Laura S Hiemcke-Jiwa, Roos J Leguit, Lars T van der Veken, Arjan Buijs, Jan Willem Leeuwis, Mirthe de Boer, N Mehdi Jiwa, Andries C Bloem, Eefke J Petersen, Roel A de Weger, Manon M H Huibers
Follicular lymphoma with progression to a high grade lymphoma bears a poor prognosis. We describe a case of a 60-year old man who presented in 2012 with an epidural mass, diagnosed as a diffuse large B-cell lymphoma (DLBCL) with concurrent low grade follicular lymphoma. Three years later, the patient presented with a cervical mass, diagnosed as a lymphoblastic lymphoma (LBL). Both the DLBCL and LBL contained a "triple hit" with BCL2, BCL6 and cMYC translocations demonstrated by fluorescence in situ hybridization analysis and a complex karyotype by SNP-array analysis...
November 17, 2016: Human Pathology
https://www.readbyqxmd.com/read/27856253/discovery-of-high-affinity-bcl6-binding-peptide-and-its-structure-activity-relationship
#7
Kotaro Sakamoto, Satoshi Sogabe, Yusuke Kamada, Nozomu Sakai, Kouhei Asano, Mie Yoshimatsu, Kou Ida, Yasuhiro Imaeda, Jun-Ichi Sakamoto
B cell lymphoma 6 (BCL6) is a transcriptional repressor that interacts with its corepressors BcoR and SMRT. Since this protein-protein interaction (PPI) induces activation and differentiation of B lymphocytes, BCL6 has been an attractive drug target for potential autoimmune disease treatments. Here we report a novel BCL6 inhibitory peptide, F1324 (Ac-LWYTDIRMSWRVP-OH), which we discovered using phage display technology; we also discuss this peptide's structure-activity relationship (SAR). For BCL6(5-129) binding, KD and IC50 values of F1324 were 0...
November 14, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27848920/burkitt-cells-on-a-peripheral-blood-smear-how-to-deal-with
#8
Marie Wyrwas, Jessica Michel, Isabelle Guibaud, Jean-François Lesesve, Blandine Bénet
The diagnosis of double hit lymphoma remains a challenge for the biologist for a good management of the patient. This new category of lymphoma "double hit" (DH) is part of a new entity of the WHO classification 2008: « Unclassifiable B lymphoma with features intermediate between diffuse large cell B lymphoma and Burkitt's lymphoma ». It is defined by the presence of a breakpoint at the locus 8q24 of the c-MYC gene associated with a recurrent translocation involving BCL2 genes primarily BCL6 or more rarely CCDN1 or BCL3 genes...
December 1, 2016: Annales de Biologie Clinique
https://www.readbyqxmd.com/read/27825111/protocol-for-qrt-pcr-analysis-from-formalin-fixed-paraffin-embedded-tissue-sections-from-diffuse-large-b-cell-lymphoma-validation-of-the-six-gene-predictor-score
#9
Nilgun Tekin, Nader Omidvar, Tim Peter Morris, Paulette Conget, Flavia Bruna, Botond Timar, Eva Gagyi, Ranjan Basak, Omkar Naik, Chirayu Auewarakul, Narongrit Sritana, Debora Levy, Juliano Julio Cerci, Sergio Paulo Bydlowski, Juliana Pereira, Mark Pierre Dimamay, Filipinas Natividad, June-Key Chung, Nevin Belder, Isinsu Kuzu, Diana Paez, Maurizio Dondi, Robert Carr, Hilal Ozdag, Rose Ann Padua
As a part of an international study on the molecular analysis of Diffuse Large B-cell Lymphoma (DLBCL), a robust protocol for gene expression analysis from RNA extraction to qRT-PCR using Formalin Fixed Paraffin Embedded tissues was developed. Here a study was conducted to define a strategy to validate the previously reported 6-gene (LMO2, BCL6, FN1, CCND2, SCYA3 and BCL2) model as predictor of prognosis in DLBCL. To avoid variation, all samples were tested in a single centre and single platform. This study comprised 8 countries (Brazil, Chile, Hungary, India, Philippines, S...
November 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27821509/approach-to-the-diagnosis-and-treatment-of-high-grade-b-cell-lymphomas-with-myc-and-bcl2-and-or-bcl6-rearrangements
#10
Pierre Sesques, Nathalie A Johnson
High grade B cell lymphomas (HGBL) with MYC and BCL2 and/or BCL6 rearrangements, so-called "double hit" lymphomas (HGBL-DH), are aggressive lymphomas that form a separate provisional entity in the 2016 revised World Heath Organization Classification of Lymphoid Tumours. Fluorescence in situ hybridization (FISH) will be required to identify HGBL-DH and will re-classify a subset of diffuse large B cell lymphomas (DLBCL) and HGBL with features intermediate between DLBCL and Burkitt lymphoma into this new category...
November 7, 2016: Blood
https://www.readbyqxmd.com/read/27815824/mir-10a-inhibits-cell-proliferation-and-promotes-cell-apoptosis-by-targeting-bcl6-in-diffuse-large-b-cell-lymphoma
#11
Qian Fan, Xiangrui Meng, Hongwei Liang, Huilai Zhang, Xianming Liu, Lanfang Li, Wei Li, Wu Sun, Haiyang Zhang, Ke Zen, Chen-Yu Zhang, Zhen Zhou, Xi Chen, Yi Ba
The BCL6 (B-Cell Lymphoma 6) gene is a proto-oncogene that is often expressed in diffuse large B-cell lymphomas (DLBCLs). BCL6 loss of function can kill DLBCL cells, demonstrating that BCL6 is necessary for the survival of DLBCL cells and could be a therapeutic target. In this study, we found that BCL6 protein levels were consistently upregulated in DLBCL tissues, whereas its mRNA levels varied randomly in tissues, suggesting that a post-transcriptional mechanism was involved in BCL6 regulation. We used bioinformatics analysis to search for miRNAs, which potentially target BCL6, and identified specific targeting sites for miR-10a in the 3'-untranslated region (3'-UTR) of BCL6...
November 4, 2016: Protein & Cell
https://www.readbyqxmd.com/read/27810071/myc-rearranged-b-cell-neoplasms-impact-of-genetics-on-classification
#12
Sabine Haberl, Torsten Haferlach, Anna Stengel, Sabine Jeromin, Wolfgang Kern, Claudia Haferlach
A cohort comprising 156 patients with B-cell neoplasms harboring an MYC rearrangement was analyzed with respect to phenotypic presentation, molecular markers (TP53, MYC and ID3) and additional cytogenetic abnormalities (concomitantly occurring BCL2, BCL6 and/or CCND1 rearrangements; double, triple or quadruple hit lymphomas = multiple hit lymphomas). MYC translocations occurred as single hit (only MYC rearranged, 63%) or multiple hit lymphoma (37%) and presented as acute leukemia (AL) (14%), Burkitt lymphoma (30%), chronic lymphocytic leukemia (CLL) (21%) or other mature B-cell neoplasms (35%)...
October 2016: Cancer Genetics
https://www.readbyqxmd.com/read/27807891/clinicopathological-features-of-primary-diffuse-large-b-cell-lymphoma-of-the-central-nervous-system-strong-ezh2-expression-implying-diagnostic-and-therapeutic-implication
#13
Shuangping Guo, Qingxian Bai, Joseph Rohr, Yingmei Wang, Yang Liu, Kaixuan Zeng, Kangjie Yu, Xiumin Zhang, Zhe Wang
Primary diffuse large B-cell lymphoma of the central nervous system (CNS DLBCL) is a rare entity which is difficult to diagnose and treat. The histone methyltransferase EZH2 was reported to be involved in the tumorigenesis of systemic DLBCL but has not been implicated in primary CNS DLBCL. The clinicopathological features of 33 cases of primary CNS DLBCL and expression of EZH2 and Y641 mutation were assessed. The tumor cells of the majority cases resembled centroblasts, and intriguingly, three cases of rare anaplastic variant were observed...
November 2, 2016: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
https://www.readbyqxmd.com/read/27806296/opposing-development-of-cytotoxic-and-follicular-helper-cd4%C3%A2-t-cells-controlled-by-the-tcf-1-bcl6-nexus
#14
Tiziano Donnarumma, George R Young, Julia Merkenschlager, Urszula Eksmond, Nadine Bongard, Stephen L Nutt, Claude Boyer, Ulf Dittmer, Vu Thuy Khanh Le-Trilling, Mirko Trilling, Wibke Bayer, George Kassiotis
CD4(+) T cells develop distinct and often contrasting helper, regulatory, or cytotoxic activities. Typically a property of CD8(+) T cells, granzyme-mediated cytotoxic T cell (CTL) potential is also exerted by CD4(+) T cells. However, the conditions that induce CD4(+) CTLs are not entirely understood. Using single-cell transcriptional profiling, we uncover a unique signature of Granzyme B (GzmB)(+) CD4(+) CTLs, which distinguishes them from other CD4(+) T helper (Th) cells, including Th1 cells, and strongly contrasts with the follicular helper T (Tfh) cell signature...
November 1, 2016: Cell Reports
https://www.readbyqxmd.com/read/27803134/gene-expression-profiling-in-blood-and-affected-muscle-tissues-reveals-differential-activation-pathways-in-patients-with-new-onset-juvenile-and-adult-dermatomyositis
#15
Consuelo M López De Padilla, Cynthia S Crowson, Molly S Hein, Richard S Pendegraft, Michael A Strausbauch, Timothy B Niewold, Floranne C Ernste, Erik Peterson, Emily C Baechler, Ann M Reed
OBJECTIVE: To identify shared and differential molecular pathways in blood and affected muscle between adult dermatomyositis (DM) and juvenile DM, and their association with clinical disease activity measures. METHODS: Gene expression of transcription factors and cytokines involved in differentiation and effector function of T cell subsets, regulatory T cells and follicular Th cells, were analyzed in the blood from 21 newly diagnosed adult and 26 juvenile DM subjects and in 15 muscle specimens (7 adult and 8 juvenile DM) using a custom RT2 Profiler PCR Array...
November 1, 2016: Journal of Rheumatology
https://www.readbyqxmd.com/read/27799148/deregulated-expression-of-hdac9-in-b-cells-promotes-development-of-lymphoproliferative-disease-and-lymphoma
#16
V S Gil, G Bhagat, L Howell, J Zhang, C H Kim, S Stengel, F Vega, A Zelent, K Petrie
Histone Deacetylase 9 (HDAC9) is expressed in B-cells and its overexpression has been observed in B-lymphoproliferative disorders and B-cell non-Hodgkin lymphomas (B-NHL). We examined HDAC9 protein expression and copy number alterations in primary B-NHL samples, identifying high HDAC9 expression among various lymphoma entities and HDAC9 copy number gains in 50% of diffuse large B-cell lymphoma (DLBCL). To study the role of HDAC9 in lymphomagenesis we generated a genetically engineered mouse (GEM) model that constitutively expressed an HDAC9 transgene throughout B-cell development under the control of the immunoglobulin heavy chain (IgH) enhancer (Eμ)...
October 28, 2016: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/27798160/water-in-oil-only-adjuvants-selectively-promote-t-follicular-helper-cell-polarization-through-a-type-i-ifn-and-il-6-dependent-pathway
#17
Nicolas Riteau, Andrea J Radtke, Kevin Shenderov, Lara Mittereder, Sandra D Oland, Sara Hieny, Dragana Jankovic, Alan Sher
T follicular helper (Tfh) cells are a subset of CD4(+) T lymphocytes that promote the development of humoral immunity. Although the triggers required for the differentiation of the other major Th subsets are well defined, those responsible for Tfh cell responses are still poorly understood. We determined that mice immunized with peptide or protein Ags emulsified in IFA or related water-in-oil adjuvants develop a highly polarized response in which the majority of the Ag-specific CD4(+) T cells are germinal center-homing CXCR5(+)Bcl6(+) Tfh cells...
November 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27776169/hepatitis-c-virus-broadly-neutralizing-monoclonal-antibodies-isolated-25-years-after-spontaneous-clearance
#18
Sabrina J Merat, Richard Molenkamp, Koen Wagner, Sylvie M Koekkoek, Dorien van de Berg, Etsuko Yasuda, Martino Böhne, Yvonne B Claassen, Bart P Grady, Maria Prins, Arjen Q Bakker, Menno D de Jong, Hergen Spits, Janke Schinkel, Tim Beaumont
Hepatitis C virus (HCV) is world-wide a major cause of liver related morbidity and mortality. No vaccine is available to prevent HCV infection. To design an effective vaccine, understanding immunity against HCV is necessary. The memory B cell repertoire was characterized from an intravenous drug user who spontaneously cleared HCV infection 25 years ago. CD27+IgG+ memory B cells were immortalized using BCL6 and Bcl-xL. These immortalized B cells were used to study antibody-mediated immunity against the HCV E1E2 glycoproteins...
2016: PloS One
https://www.readbyqxmd.com/read/27773559/immunophenotypic-and-genetic-characteristics-of-diffuse-large-b-cell-lymphoma-in-taiwan
#19
Sheng-Tsung Chang, Shang-Wen Chen, Chung-Han Ho, Chun-Chi Kuo, Seiji Sakata, Kengo Takeuchi, Shih-Sung Chuang
BACKGROUND/PURPOSE: Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma type. The immunophenotypic and genetic features of DLBCL in Taiwan have not been characterized. METHODS: In this study, we performed immunohistochemical analysis and interphase fluorescence in situ hybridization (FISH) using tissue microarray sections to investigate a cohort of unselected DLBCL cases in a single institution in Taiwan from 1990 to 2010. RESULTS: Of the 153 cases investigated, CD10, bcl-6, and MUM1 were expressed in 16...
October 20, 2016: Journal of the Formosan Medical Association, Taiwan Yi Zhi
https://www.readbyqxmd.com/read/27764808/the-feedback-loop-of-litaf-and-bcl6-is-involved-in-regulating-apoptosis-in-b-cell-non-hodgkin-s-lymphoma
#20
Yaoyao Shi, Yue Kuai, Lizhen Lei, Yuanyuan Weng, Friederike Berberich-Siebelt, Xinxia Zhang, Jinjie Wang, Yuan Zhou, Xin Jiang, Guoping Ren, Hongyang Pan, Zhengrong Mao, Ren Zhou
Dysregulation of the apoptotic pathway is widely recognized as a key step in lymphomagenesis. Notably, LITAF was initially identified as a p53-inducible gene, subsequently implicated as a tumor suppressor. Our previous study also showed LITAF to be methylated in 89.5% B-NHL samples. Conversely, deregulated expression of BCL6 is a pathogenic event in many lymphomas. Interestingly, our study found an oppositional expression of LITAF and BCL6 in B-NHL. In addition, LITAF was recently identified as a novel target gene of BCL6...
October 15, 2016: Oncotarget
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