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lymphomagenesis

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https://www.readbyqxmd.com/read/29143824/pd-1-is-a-haploinsufficient-suppressor-of-t-cell-lymphomagenesis
#1
Tim Wartewig, Zsuzsanna Kurgyis, Selina Keppler, Konstanze Pechloff, Erik Hameister, Rupert Öllinger, Roman Maresch, Thorsten Buch, Katja Steiger, Christof Winter, Roland Rad, Jürgen Ruland
T cell non-Hodgkin lymphomas are a heterogeneous group of highly aggressive malignancies with poor clinical outcomes. T cell lymphomas originate from peripheral T cells and are frequently characterized by genetic gain-of-function variants in T cell receptor (TCR) signalling molecules. Although these oncogenic alterations are thought to drive TCR pathways to induce chronic proliferation and cell survival programmes, it remains unclear whether T cells contain tumour suppressors that can counteract these events...
November 15, 2017: Nature
https://www.readbyqxmd.com/read/29141798/ecotropic-viral-integration-site-5-evi5-variants-are-associated-with-multiple-sclerosis-in-iranian-population
#2
Mehrdokht Mazdeh, Soudeh Ghafouri-Fard, Rezvan Noroozi, Arezou Sayad, Maryam Khani, Mohammad Taheri, Mir Davood Omrani
BACKGROUND: Multiple sclerosis (MS) is a multifactorial disorder with immunological basis. Numerous genetic and environmental factors contribute in its pathogenesis. Several genetic loci have been shown to be associated with MS risk. Among genes whose participation in MS has been evaluated is Ecotropic Viral Integration Site 5 (EVI5). EVI5 is a common site of retroviral integration with a possible role in T-cell lymphomagenesis. METHODS: In the current study, we aimed to confirm association of the single nucleotide polymorphisms (SNPs) within EVI5 gene with MS in 410 relapsing-remitting MS patients and 410 controls from Iranian population...
November 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/29137176/ebv-and-apoptosis-the-viral-master-regulator-of-cell-fate
#3
REVIEW
Leah Fitzsimmons, Gemma L Kelly
Epstein-Barr virus (EBV) was first discovered in cells from a patient with Burkitt lymphoma (BL), and is now known to be a contributory factor in 1-2% of all cancers, for which there are as yet, no EBV-targeted therapies available. Like other herpesviruses, EBV adopts a persistent latent infection in vivo and only rarely reactivates into replicative lytic cycle. Although latency is associated with restricted patterns of gene expression, genes are never expressed in isolation; always in groups. Here, we discuss (1) the ways in which the latent genes of EBV are known to modulate cell death, (2) how these mechanisms relate to growth transformation and lymphomagenesis, and (3) how EBV genes cooperate to coordinately regulate key cell death pathways in BL and lymphoblastoid cell lines (LCLs)...
November 13, 2017: Viruses
https://www.readbyqxmd.com/read/29132323/integrative-microrna-and-mrna-deep-sequencing-expression-profiling-in-endemic-burkitt-lymphoma
#4
Cliff I Oduor, Yasin Kaymaz, Kiprotich Chelimo, Juliana A Otieno, John Michael Ong'echa, Ann M Moormann, Jeffrey A Bailey
BACKGROUND: Burkitt lymphoma (BL) is characterized by overexpression of the c-myc oncogene, which in the vast majority of cases is a consequence of an IGH/MYC translocation. While myc is the seminal event, BL is a complex amalgam of genetic and epigenetic changes causing dysregulation of both coding and non-coding transcripts. Emerging evidence suggest that abnormal modulation of mRNA transcription via miRNAs might be a significant factor in lymphomagenesis. However, the alterations in these miRNAs and their correlations to their putative mRNA targets have not been extensively studied relative to normal germinal center (GC) B cells...
November 13, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29097774/altered-b-lymphopoiesis-in-mice-with-deregulated-thrombopoietin-signaling
#5
Amanda E Au, Marion Lebois, Starling A Sim, Ping Cannon, Jason Corbin, Pradnya Gangatirkar, Craig D Hyland, Diane Moujalled, Angelika Rutgersson, Fatme Yassinson, Benjamin T Kile, Kylie D Mason, Ashley P Ng, Warren S Alexander, Emma C Josefsson
Thrombopoietin (TPO) is the master cytokine regulator of megakaryopoiesis. In addition to regulation of megakaryocyte and platelet number, TPO is important for maintaining proper hematopoietic stem cell (HSC) function. It was previously shown that a number of lymphoid genes were upregulated in HSCs from Tpo (-/-) mice. We investigated if absent or enhanced TPO signaling would influence normal B-lymphopoiesis. Absent TPO signaling in Mpl (-/-) mice led to enrichment of a common lymphoid progenitor (CLP) signature in multipotential lineage-negative Sca-1(+)c-Kit(+) (LSK) cells and an increase in CLP formation...
November 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29080214/transcription-factor-yy1-can-control-aid-mediated-mutagenesis-in-mice
#6
Kristina Zaprazna, Arindam Basu, Nikola Tom, Vibha Jha, Suchita Hodawadekar, Lenka Radova, Jitka Malcikova, Boris Tichy, Sarka Pospisilova, Michael L Atchison
Activation-induced cytidine deminase (AID) is crucial for controlling the immunoglobulin (Ig) diversification processes of somatic hypermutation (SHM) and class switch recombination (CSR). AID initiates these processes by deamination of cytosine, ultimately resulting in mutations or double strand DNA breaks needed for SHM and CSR. Levels of AID control mutation rates, and off-target non-Ig gene mutations can contribute to lymphomagenesis. Therefore, factors that control AID levels in the nucleus can regulate SHM and CSR, and may contribute to disease...
October 28, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29074502/ebv-latent-membrane-protein-2a-orchestrates-p27-kip1-degradation-via-cks1-to-accelerate-myc-driven-lymphoma-in-mice
#7
Kamonwan Fish, Richard P Sora, Samantha J Schaller, Richard Longnecker, Masato Ikeda
Epstein-Barr virus (EBV) establishes lifelong infection in B lymphocytes of most human hosts and is associated with several B lymphomas. During latent infection, EBV encodes latent membrane protein 2A (LMP2A) to promote survival of B cells by mimicking host B-cell receptor (BCR) signaling. Studying the roles of LMP2A during lymphoma development in vivo, we found that LMP2A mediates rapid MYC-driven lymphoma onset by allowing B cells to bypass MYC-induced apoptosis mediated by the p53 pathway in our transgenic mouse model...
October 26, 2017: Blood
https://www.readbyqxmd.com/read/29071477/enforced-expression-of-mir142-a-target-of-chromosome-translocation-in-human-b-cell-tumors-results-in-b-cell-depletion
#8
Kodai Kuriyama, Yutaka Enomoto, Ritsuro Suzuki, Jyuri Watanuki, Hiroki Hosoi, Yusuke Yamashita, Shogo Murata, Toshiki Mushino, Shinobu Tamura, Nobuyoshi Hanaoka, Martin Dyer, Reiner Siebert, Hiroshi Kiyonari, Hideki Nakakuma, Toshio Kitamura, Takashi Sonoki
MicroRNA142 (MIR142) is a target of chromosome translocations and mutations in human B-cell lymphomas. We analyzed an aggressive B-cell lymphoma carrying t(8;17)(q24;q22) and t(6;14)(p21;q32), and sought to explore the role(s) of MIR142 in lymphomagenesis. t(8;17)(q24;q22) involved MYC on 8q24 and pri-MIR142 on 17q22. MYC was activated by a promoter substitution by t(8;17)(q24;q22). t(8;17)(q24;q22) was an additional event after t(6;14) (p21;q32), which caused the over-expression of CCND3. Southern blot analyses revealed that the MIR142 locus was deleted from the affected allele, whereas Northern analyses showed over-expression of MIR142 in tumor cells...
October 25, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/29070995/dramatic-response-with-single-agent-ibrutinib-in-multiply-relapsed-marginal-zone-lymphoma-with-myd88-l265p-mutation
#9
Ryan C Lynch, Ranjana H Advani
The B-cell receptor signaling pathway is important in the lymphomagenesis of many lymphomas, including marginal zone lymphoma (MZL). Herein we describe a case of extranodal MZL refractory to multiple lines of therapy. The presence of an IgM paraprotein prompted further evaluation, and the patient was found to have an MYD88(L265P) mutation. Treatment with ibrutinib led to a dramatic response with prompt resolution of symptoms and significant improvement in measurable sites of disease. The excellent response to ibrutinib in our patient with MYD88(L265P)-mutated refractory MZL supports a biological rationale for its use...
September 2017: Case Reports in Oncology
https://www.readbyqxmd.com/read/29052132/current-progress-in-ebv-associated-b-cell-lymphomas
#10
Yonggang Pei, Alexandria E Lewis, Erle S Robertson
Epstein-Barr virus (EBV) was the first human tumor virus discovered more than 50 years ago. EBV-associated lymphomagenesis is still a significant viral-associated disease as it involves a diverse range of pathologies, especially B-cell lymphomas. Recent development of high-throughput next-generation sequencing technologies and in vivo mouse models have significantly promoted our understanding of the fundamental molecular mechanisms which drive these cancers and allowed for the development of therapeutic intervention strategies...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29041946/the-role-of-b-cell-antigen-receptors-in-mantle-cell-lymphoma
#11
REVIEW
Michael Fichtner, Martin Dreyling, Mascha Binder, Martin Trepel
Mantle cell lymphoma (MCL) is characterized by an aggressive clinical course and secondary resistance to currently available therapies in most cases. Therefore, despite recent advances in the treatment of this disease, it is still considered to be incurable in the majority of cases. MCL B cells retain their B cell antigen receptor (BCR) expression during and after neoplastic transformation. BCRs in MCL show distinct patterns of antigen selection and ongoing BCR signaling. However, little is known about the involved antigens and the mechanisms leading to lymphomagenesis and lymphoma progression in MCL...
October 17, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29034060/activation-of-the-aryl-hydrocarbon-receptor-and-risk-of-lymphoma-subtypes
#12
Sonia Sanna, Giannina Satta, Marina Padoan, Sara Piro, Angela Gambelunghe, Lucia Miligi, Giovanni Maria Ferri, Corrado Magnani, Giacomo Muzi, Luigi Rigacci, Maria Giuseppina Cabras, Emanuele Angelucci, Gian Carlo Latte, Attilio Gabbas, Maria Grazia Ennas, Pierluigi Cocco
The aryl hydrocarbon receptor (AhR) is a transcription factor implicated in several pathways known to be relevant in lymphomagenesis. Aim of our study was to explore the link between AhR activation and risk of lymphoma subtypes. We used a Dual-Luciferase Assay(®) and a luminometer to detect the activation of the luciferase gene, in HepG2 cells transfected with a specific reporter systems, by a 50 ml serum aliquot of cases of diffuse large B cell lymphoma (N = 108), follicular lymphoma (N = 85), chronic lymphocytic leukemia (N = 72), multiple myeloma (N = 80), and Hodgkin lymphoma (N = 94) and 357 controls who participated in the multicentre Italian study on gene-environment interactions in lymphoma etiology (ItGxE)...
2017: International Journal of Molecular Epidemiology and Genetics
https://www.readbyqxmd.com/read/28983187/viral-causes-of-lymphoma-the-history-of-epstein-barr-virus-and-human-t-lymphotropic-virus-1
#13
REVIEW
Daniel Esau
In 1964, Epstein, Barr, and Achong published a report outlining their discovery of viral particles in lymphoblasts isolated from a patient with Burkitt lymphoma. The Epstein-Barr virus (EBV) was the first human cancer virus to be described, and its discovery paved the way for further investigations into the oncogenic potential of viruses. In the decades following the discovery of EBV, multinational research efforts led to the discovery of further viral causes of various human cancers. Lymphomas are perhaps the cancer type that is most closely associated with oncogenic viruses: infection with EBV, human T-lymphotropic virus 1 (HTLV-1), human immunodeficiency virus (HIV), Kaposi sarcoma-associated herpesvirus/human herpesvirus 8, and hepatitis C virus have all been associated with lymphomagenesis...
2017: Virology: Research and Treatment
https://www.readbyqxmd.com/read/28978699/induction-of-dna-damages-upon-marek-s-disease-virus-infection-implication-in-viral-replication-and-pathogenesis
#14
Djihad Bencherit, Sylvie Remy, Yves Le Vern, Tereza Vychodil, Luca D Bertzbach, Benedikt B Kaufer, Caroline Denesvre, Laëtitia Trapp-Fragnet
Marek's disease virus (MDV) is a highly contagious alphaherpesvirus that infects chickens and causes a deadly neoplastic disease. We previously demonstrated that MDV infection arrests cells in S-phase and that the tegument protein VP22 plays a major role in this process. In addition, expression of VP22 induces double strand breaks (DSB) in the cellular DNA, suggesting that DNA damage and the associated cellular response might be favorable for the MDV lifecycle. Here, we addressed the role of DNA damage in MDV replication and pathogenesis...
October 4, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28953617/effects-of-microrna-21-on-apoptosis-by-regulating-the-expression-of-pten-in-diffuse-large-b-cell-lymphoma
#15
Jia Song, Qing Shao, Chunhong Li, Hui Liu, Jing Li, Yihao Wang, Wenjing Song, Lijuan Li, Guojin Wang, Zonghong Shao, Rong Fu
Diffuse large B-cell lymphoma (DLBCL) is an aggressive malignancy and the most common subtype of non-Hodgkin lymphoma in China. However, many cases still remain biologically and clinically heterogeneous, indicating that the DLBCL mechanism remains unclear. MicroRNAs (miRNAs) are critically responsible for lymphomagenesis. We found that plasma miR-21 level was significantly higher in B-cell lymphoma. However, the exact contribution of miR-21 in DLBCL remains unknown.To determine the function and mechanism of miR-21 in DLBCL, miR-21 and phosphatase and tensin homolog (PTEN) expressions were examined through real-time PCR and immunohistochemical methods...
September 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28949959/hepatitis-c-virus-positive-diffuse-large-b-cell-lymphomas-have-distinct-molecular-features-and-lack-bcl2-translocations
#16
Carlo Visco, Jinfen Wang, Maria Chiara Tisi, Lijuan Deng, Emanuele S G D'Amore, Alexandar Tzankov, Santiago Montes-Moreno, Karen Dybkær, Govind Bhagat, Eric D Hsi, J Han van Krieken, Maurilio Ponzoni, Andrés J M Ferreri, Michael B Møller, Miguel A Piris, L Jeffrey Medeiros, Zijun Y Xu-Monette, Ken H Young
BACKGROUND: The clinical presentation of patients with hepatitis C virus (HCV)-positive diffuse large B-cell lymphoma (DLBCL) is different from their HCV-negative counterparts, but the underlying molecular and pathological characteristics are largely under investigated. The virus has a role in lymphomagenesis, as witnessed by the curative potential of antiviral therapy in HCV-related low-grade B-cell lymphomas. METHODS: We performed a case-control study including 44 HCV-positive cases of de novo DLBCL, comparing them with 132 HCV-negative patients as controls (ratio 3 to 1)...
September 26, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28922373/dynein-light-chain-regulates-adaptive-and-innate-b-cell-development-by-distinctive-genetic-mechanisms
#17
Ashleigh King, Lingli Li, David M Wong, Rui Liu, Rebecca Bamford, Andreas Strasser, David M Tarlinton, Jörg Heierhorst
Mechanistic differences in the development and function of adaptive, high-affinity antibody-producing B-2 cells and innate-like, "natural" antibody-producing B-1a cells remain poorly understood. Here we show that the multi-functional dynein light chain (DYNLL1/LC8) plays important roles in the establishment of B-1a cells in the peritoneal cavity and in the ongoing development of B-2 lymphoid cells in the bone marrow of mice. Epistasis analyses indicate that Dynll1 regulates B-1a and early B-2 cell development in a single, linear pathway with its direct transcriptional activator ASCIZ (ATMIN/ZNF822), and that the two genes also have complementary functions during late B-2 cell development...
September 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28893938/epstein-barr-virus-associated-lymphomas
#18
REVIEW
Claire Shannon-Lowe, Alan B Rickinson, Andrew I Bell
Epstein-Barr virus (EBV), originally discovered through its association with Burkitt lymphoma, is now aetiologically linked to a remarkably wide range of lymphoproliferative lesions and malignant lymphomas of B-, T- and NK-cell origin. Some occur as rare accidents of virus persistence in the B lymphoid system, while others arise as a result of viral entry into unnatural target cells. The early finding that EBV is a potent B-cell growth transforming agent hinted at a simple oncogenic mechanism by which this virus could promote lymphomagenesis...
October 19, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28892044/a-novel-mouse-model-of-rhabdomyosarcoma-underscores-the-dichotomy-of-mdm2-alt1-function-in-vivo
#19
D F Comiskey, A G Jacob, B L Sanford, M Montes, A K Goodwin, H Steiner, E Matsa, A S Tapia-Santos, T W Bebee, J Grieves, K La Perle, P Boyaka, D S Chandler
Alternative splicing of the oncogene murine double minute 2 (MDM2) is induced in response to genotoxic stress. MDM2-ALT1, the major splice variant generated, is known to activate the p53 pathway and impede full-length MDM2's negative regulation of p53. Despite this perceptible tumor-suppressive role, MDM2-ALT1 is also associated with several cancers. Furthermore, expression of MDM2-ALT1 has been observed in aggressive metastatic disease in pediatric rhabdomyosarcoma (RMS), irrespective of histological subtype...
September 11, 2017: Oncogene
https://www.readbyqxmd.com/read/28885612/understanding-cd30-biology-and-therapeutic-targeting-a-historical-perspective-providing-insight-into-future-directions
#20
REVIEW
C A van der Weyden, S A Pileri, A L Feldman, J Whisstock, H M Prince
CD30 is a member of the tumor necrosis factor receptor superfamily. It is characteristically expressed in certain hematopoietic malignancies, including anaplastic large cell lymphoma and Hodgkin lymphoma, among others. The variable expression of CD30 on both normal and malignant lymphoid cells has focused research efforts on understanding the pathogenesis of CD30 upregulation, its contribution to lymphomagenesis through anti-apoptotic mechanisms, and its effect on cell survival. Given the restriction of CD30 to certain tumor types, the logical extension of this has been to attempt to exploit it as a therapeutic target...
September 8, 2017: Blood Cancer Journal
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