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lymphomagenesis

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https://www.readbyqxmd.com/read/28088785/the-igh-locus-3-cis-regulatory-super-enhancer-co-opts-aid-for-allelic-transvection
#1
Sandrine Le Noir, Brice Laffleur, Claire Carrion, Armand Garot, Sandrine Lecardeur, Eric Pinaud, Yves Denizot, Jane Skok, Michel Cogné
Immunoglobulin heavy chain (IgH) alleles have ambivalent relationships: they feature both allelic exclusion, ensuring monoallelic expression of a single immunoglobulin (Ig) allele, and frequent inter-allelic class-switch recombination (CSR) reassembling genes from both alleles. The IgH locus 3' regulatory region (3'RR) includes several transcriptional cis-enhancers promoting activation-induced cytidine deaminase (AID)-dependent somatic hypermutation (SHM) and CSR, and altogether behaves as a strong super-enhancer...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28072889/in-depth-analysis-of-compartmentalization-of-hiv-1-matrix-protein-p17-in-pbmc-and-plasma
#2
Marina Selleri, Riccardo Dolcetti, Francesca Caccuri, Emanuela Giombini, Gabriella Rozera, Isabella Abbate, Alessia Mammone, Stefania Zanussi, Debora Martorelli, Simona Fiorentini, Arnaldo Caruso, Maria Rosaria Capobianchi
HIV-1 p17 plays an important role in the virus life-cycle and disease pathogenesis. Recent studies indicated a high heterogeneity of p17. A high number of insertions in the p17 carboxy-terminal region have been more frequently detected in patients with non-Hodgkin lymphoma (NHL), suggesting a role of altered p17 in lymphomagenesis. Based on p17 heterogeneity, possible PBMC/plasma compartmentalization of p17 variants was explored by ultra-deep pyrosequencing in five NHL patients. The high variability of p17 with insertions at the carboxy-terminal region was confirmed in plasma and observed for the first time in proviral genomes...
January 9, 2017: New Microbiologica
https://www.readbyqxmd.com/read/28069569/the-crebbp-acetyltransferase-is-a-haploinsufficient-tumor-suppressor-in-b-cell-lymphoma
#3
Jiyuan Zhang, Sofija Vlasevska, Victoria A Wells, Sarah Nataraj, Antony B Holmes, Romain Duval, Stefanie N Meyer, Tongwei Mo, Katia Basso, Paul K Brindle, Shafinaz Hussein, Riccardo Dalla-Favera, Laura Pasqualucci
Inactivating mutations of the CREBBP acetyltransferase are highly frequent in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL), the two most common germinal-center (GC) derived cancers. However, the role of CREBBP inactivation in lymphomagenesis remains unclear. Here we show that CREBBP regulates enhancer/super-enhancer networks with central roles in GC/post-GC cell fate decisions, including genes involved in signal transduction by the B-cell receptor and CD40 receptor, transcriptional control of GC and plasma cell development, and antigen presentation...
January 9, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/27982060/a-crispr-cas9-functional-screen-identifies-rare-tumor-suppressors
#4
Alexandra Katigbak, Regina Cencic, Francis Robert, Patrick Sénécha, Claudio Scuoppo, Jerry Pelletier
An enormous amount of tumor sequencing data has been generated through large scale sequencing efforts. The functional consequences of the majority of mutations identified by such projects remain an open, unexplored question. This problem is particularly complicated in the case of rare mutations where frequency of occurrence alone or prediction of functional consequences are insufficient to distinguish driver from passenger or bystander mutations. We combine genome editing technology with a powerful mouse cancer model to uncover previously unsuspected rare oncogenic mutations in Burkitt's lymphoma...
December 16, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27982024/epstein-barr-virus-positive-follicular-lymphoma
#5
Nicholas Mackrides, German Campuzano-Zuluaga, Yvan Maque-Acosta, Adrienne Moul, Nouf Hijazi, Francis Offiong Ikpatt, Ronald Levy, Ramiro E Verdun, Kranthi Kunkalla, Yasodha Natkunam, Izidore S Lossos, Francisco Vega, Jennifer Chapman
Epstein-Barr virus (EBV) -associated follicular lymphoma is only rarely reported. Herein, we report the largest series analyzing prevalence and clinicopathologic characteristics of EBV-associated follicular lymphoma occurring in unselected cases. Out of 382 analyzed cases, 10 EBV-positive follicular lymphomas were identified (prevalence=2.6%, 95% confidence interval 1.3-4.0%). All EBV-positive follicular lymphomas showed EBV-encoded small RNA-positive lymphoma cells present in a follicular distribution. Of these, eight also had tissue available for testing of expression of latent membrane protein 1 (LMP1), out of which six (75%) were positive...
December 16, 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/27913676/translational-control-by-mtor-independent-routes-how-eif6-organizes-metabolism
#6
REVIEW
Annarita Miluzio, Sara Ricciardi, Nicola Manfrini, Roberta Alfieri, Stefania Oliveto, Daniela Brina, Stefano Biffo
Over the past few years, there has been a growing interest in the interconnection between translation and metabolism. Important oncogenic pathways, like those elicited by c-Myc transcription factor and mTOR kinase, couple the activation of the translational machinery with glycolysis and fatty acid synthesis. Eukaryotic initiation factor 6 (eIF6) is a factor necessary for 60S ribosome maturation. eIF6 acts also as a cytoplasmic translation initiation factor, downstream of growth factor stimulation. eIF6 is up-regulated in several tumor types...
December 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27909217/the-small-foxp1-isoform-predominantly-expressed-in-activated-b-cell-like-diffuse-large-b-cell-lymphoma-and-full-length-foxp1-exert-similar-oncogenic-and-transcriptional-activity-in-human-b-cells
#7
Martine van Keimpema, Leonie J Grüneberg, Esther J M Schilder-Tol, Monique E C M Oud, Esther Beuling, Paul J Hensbergen, Johann de Jong, Steven T Pals, Marcel Spaargaren
The forkhead transcription factor FOXP1 is generally regarded as an oncogene in activated B cell-like diffuse large B-cell lymphoma. Previous studies have suggested that a small isoform of FOXP1 (FOXP1-iso), rather than full-length FOXP1 (FOXP1-FL), may possess this oncogenic activity. Corroborating those studies, we here show that activated B cell-like diffuse large B-cell lymphoma cell-lines and primary activated B cell-like diffuse large B-cell lymphoma cells predominantly express FOXP1-iso and that the 5-end of the Foxp1 gene is a common insertion site in murine lymphomas in leukaemia virus- and transposon-mediated insertional mutagenesis screens...
December 1, 2016: Haematologica
https://www.readbyqxmd.com/read/27894215/the-molecular-pathogenesis-of-mantle-cell-lymphoma
#8
Niklas Vogt, Beiying Dai, Tabea Erdmann, Wolfgang E Berdel, Georg Lenz
Mantle cell lymphoma (MCL) is characterized by the translocation t(11;14) leading to constitutive cyclin D1 overexpression. However, overexpression of cyclin D1 alone is insufficient to cause malignant transformation. Secondary genetic alterations and deregulated signaling pathways involved in DNA damage response, cell proliferation, and apoptosis are indispensable for MCL lymphomagenesis. Recent studies investigating the biology of MCL have revealed crucial importance of B-cell receptor (BCR), nuclear factor-kappa B (NF-κB), phosphoinositide 3-kinase (PI3K), and BCL2 signaling for the molecular pathogenesis of MCL...
November 28, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27886133/epigenetic-impact-on-ebv-associated-b-cell-lymphomagenesis
#9
REVIEW
Shatadru Ghosh Roy, Erle S Robertson, Abhik Saha
Epigenetic modifications leading to either transcriptional repression or activation, play an indispensable role in the development of human cancers. Epidemiological study revealed that approximately 20% of all human cancers are associated with tumor viruses. Epstein-Barr virus (EBV), the first human tumor virus, demonstrates frequent epigenetic alterations on both viral and host genomes in associated cancers-both of epithelial and lymphoid origin. The cell type-dependent different EBV latent gene expression patterns appear to be determined by the cellular epigenetic machinery and similarly viral oncoproteins recruit epigenetic regulators in order to deregulate the cellular gene expression profile resulting in several human cancers...
November 24, 2016: Biomolecules
https://www.readbyqxmd.com/read/27869314/runx1-orchestrates-sphingolipid-metabolism-and-glucocorticoid-resistance-in-lymphomagenesis
#10
A Kilbey, A Terry, S Wotton, G Borland, Q Zhang, N Mackay, A McDonald, M Bell, M J O Wakelam, E R Cameron, J C Neil
The three-membered RUNX gene family includes RUNX1, a major mutational target in human leukemias, and displays hallmarks of both tumor suppressors and oncogenes. In mouse models, the Runx genes appear to act as conditional oncogenes, as ectopic expression is growth suppressive in normal cells but drives lymphoma development potently when combined with over-expressed Myc or loss of p53. Clues to underlying mechanisms emerged previously from murine fibroblasts where ectopic expression of any of the Runx genes promotes survival through direct and indirect regulation of key enzymes in sphingolipid metabolism associated with a shift in the "sphingolipid rheostat" from ceramide to sphingosine-1-phosphate (S1P)...
November 21, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27846393/decoding-the-dna-methylome-of-mantle-cell-lymphoma-in-the-light-of-the-entire-b-cell-lineage
#11
Ana C Queirós, Renée Beekman, Roser Vilarrasa-Blasi, Martí Duran-Ferrer, Guillem Clot, Angelika Merkel, Emanuele Raineri, Nuria Russiñol, Giancarlo Castellano, Sílvia Beà, Alba Navarro, Marta Kulis, Núria Verdaguer-Dot, Pedro Jares, Anna Enjuanes, María José Calasanz, Anke Bergmann, Inga Vater, Itziar Salaverría, Harmen J G van de Werken, Wyndham H Wilson, Avik Datta, Paul Flicek, Romina Royo, Joost Martens, Eva Giné, Armando Lopez-Guillermo, Hendrik G Stunnenberg, Wolfram Klapper, Christiane Pott, Simon Heath, Ivo G Gut, Reiner Siebert, Elías Campo, José I Martín-Subero
We analyzed the in silico purified DNA methylation signatures of 82 mantle cell lymphomas (MCL) in comparison with cell subpopulations spanning the entire B cell lineage. We identified two MCL subgroups, respectively carrying epigenetic imprints of germinal-center-inexperienced and germinal-center-experienced B cells, and we found that DNA methylation profiles during lymphomagenesis are largely influenced by the methylation dynamics in normal B cells. An integrative epigenomic approach revealed 10,504 differentially methylated regions in regulatory elements marked by H3K27ac in MCL primary cases, including a distant enhancer showing de novo looping to the MCL oncogene SOX11...
November 14, 2016: Cancer Cell
https://www.readbyqxmd.com/read/27806371/lymphadenectomy-specimens-in-a-large-retrospective-cohort-of-pediatric-patients-reveal-no-in-situ-lymphomas-but-a-broad-spectrum-of-reactive-changes
#12
Yara Banz, Alexandar Tzankov, Stephan Dirnhofer, Aurel Perren, Sylvia Hoeller
OBJECTIVES: While the incidence and prevalence of in situ follicular neoplasia (ISFN) and in situ mantle cell neoplasia (ISMCN) in adults are well documented, little is known about these early (precursor) lesions in pediatric populations. The aim of this study was to analyze so-called 'reactive' lymph nodes harvested for the purpose of staging solid tumors, unexplained lymphadenopathies, or presumed inflammatory processes or in conjunction with other surgical interventions in children and adolescents aged <18 years, with special attention to ISFN and ISMCN...
November 3, 2016: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27799525/expression-of-hiv-1-matrix-protein-p17-and-association-with-b-cell-lymphoma-in-hiv-1-transgenic-mice
#13
Virginia A Carroll, Mark K Lafferty, Luigi Marchionni, Joseph L Bryant, Robert C Gallo, Alfredo Garzino-Demo
HIV-1 infection is associated with increased risk for B-cell lymphomas. How HIV infection promotes the development of lymphoma is unclear, but it may involve chronic B-cell activation, inflammation, and/or impaired immunity, possibly leading to a loss of control of oncogenic viruses and reduced tumor immunosurveillance. We hypothesized that HIV structural proteins may contribute to lymphomagenesis directly, because they can persist long term in lymph nodes in the absence of viral replication. The HIV-1 transgenic mouse Tg26 carries a noninfectious HIV-1 provirus lacking part of the gag-pol region, thus constituting a model for studying the effects of viral products in pathogenesis...
November 15, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27799148/deregulated-expression-of-hdac9-in-b-cells-promotes-development-of-lymphoproliferative-disease-and-lymphoma-in-mice
#14
Veronica S Gil, Govind Bhagat, Louise Howell, Jiyuan Zhang, Chae H Kim, Sven Stengel, Francisco Vega, Arthur Zelent, Kevin Petrie
Histone deacetylase 9 (HDAC9) is expressed in B cells, and its overexpression has been observed in B-lymphoproliferative disorders, including B-cell non-Hodgkin lymphoma (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)...
December 1, 2016: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/27797382/defective-replication-stress-response-inhibits-lymphomagenesis-and-impairs-lymphocyte-reconstitution
#15
M V Puccetti, M A Fischer, M P Arrate, K L Boyd, R J Duszynski, R Bétous, D Cortez, C M Eischen
DNA replication stress promotes genome instability in cancer. However, the contribution of the replication stress response to the development of malignancies remains unresolved. The DNA replication stress response protein SMARCAL1 stabilizes DNA replication forks and prevents replication fork collapse, a cause of DNA breaks and apoptosis. While the fork regression/remodeling functions of SMARCAL1 have been investigated, its in vivo functions in replication stress and cancer are unclear. Using a gamma radiation (IR)-induced replication stress T-cell lymphoma mouse model, we observed a significant inhibition of lymphomagenesis in mice lacking one or both alleles of Smarcal1...
October 31, 2016: Oncogene
https://www.readbyqxmd.com/read/27795529/how-does-htlv-1-induce-atl
#16
Masao Matsuoka
Human T-cell leukemia virus type 1 (HTLV-1) spreads through cell-to-cell transmission in vivo. HTLV-1 mainly infects CD4+ T cells in vivo. Viral genes enable infected cells to proliferate and escape detection by the host immune system. HTLV-1 infected cells tend to infiltrate tissues, and enter breast milk and semen, thereby infecting a new host. HTLV-1 bZIP factor (HBZ) causes overproduction of interferon gamma, which is associated with inflammation and lymphomagenesis. Thus, the strategies by which HTLV-1 proliferates and survives in infected cells are promoted, which is thought to induce ATL and inflammatory diseases in infected individuals...
2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
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
#17
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
https://www.readbyqxmd.com/read/27755151/epstein-barr-virus-associated-lymphomas-in-people-with-hiv
#18
Antonino Carbone, Chiara C Volpi, Ambra V Gualeni, Annunziata Gloghini
PURPOSE OF REVIEW: The present review summarizes the association of the different histotypes of Epstein-Barr virus (EBV)-associated lymphomas with known genetic lesions and/or oncogenic viruses. A more comprehensive understanding of the complex interplay existing between genetic abnormalities of tumor cells and the viral contribution to the development of EBV-associated lymphomas is pivotal for the development of more effective treatments. RECENT FINDINGS: Recent evidence indicates that HIV may contribute to lymphomagenesis by acting directly on B lymphocytes as a critical microenvironmental factor...
January 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/27741509/mek1-is-required-for-the-development-of-nras-driven-leukemia
#19
Joanna D Nowacka, Christian Baumgartner, Cristiana Pelorosso, Mareike Roth, Johannes Zuber, Manuela Baccarini
The dual-specificity kinases MEK1 and MEK2 act downstream of RAS/RAF to induce ERK activation, which is generally considered protumorigenic. Activating MEK mutations have not been discovered in leukemia, in which pathway activation is caused by mutations in upstream components such as RAS or Flt3. The anti-leukemic potential of MEK inhibitors is being tested in clinical trials; however, downregulation of MEK1 promotes Eμ-Myc-driven lymphomagenesis and MEK1 ablation induces myeloproliferative disease in mice, raising the concern that MEK inhibitors may be inefficient or counterproductive in this context...
October 10, 2016: Oncotarget
https://www.readbyqxmd.com/read/27733359/crebbp-inactivation-promotes-the-development-of-hdac3-dependent-lymphomas
#20
Yanwen Jiang, Ana Ortega-Molina, Huimin Geng, Hsia-Yuan Ying, Katerina Hatzi, Sara Parsa, Dylan McNally, Ling Wang, Ashley S Doane, Xabier Agirre, Matt Teater, Cem Meydan, Zhuoning Li, David Poloway, Shenqiu Wang, Daisuke Ennishi, David W Scott, Kristy R Stengel, Janice E Kranz, Edward Holson, Sneh Sharma, James W Young, Chi-Shuen Chu, Robert G Roeder, Rita Shaknovich, Scott W Hiebert, Randy D Gascoyne, Wayne Tam, Olivier Elemento, Hans-Guido Wendel, Ari M Melnick
: Somatic mutations in CREBBP occur frequently in B-cell lymphoma. Here, we show that loss of CREBBP facilitates the development of germinal center (GC)-derived lymphomas in mice. In both human and murine lymphomas, CREBBP loss-of-function resulted in focal depletion of enhancer H3K27 acetylation and aberrant transcriptional silencing of genes that regulate B-cell signaling and immune responses, including class II MHC. Mechanistically, CREBBP-regulated enhancers are counter-regulated by the BCL6 transcriptional repressor in a complex with SMRT and HDAC3, which we found to bind extensively to MHC class II loci...
January 2017: Cancer Discovery
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