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https://www.readbyqxmd.com/read/27030389/genetic-basis-of-pd-l1-overexpression-in-diffuse-large-b-cell-lymphomas
#1
Konstantinos Georgiou, Longyun Chen, Mattias Berglund, Weicheng Ren, Noel F C C de Miranda, Susana Lisboa, Marco Fangazio, Shida Zhu, Yong Hou, Kui Wu, Wenfeng Fang, Xianhuo Wang, Bin Meng, Li Zhang, Yixin Zeng, Govind Bhagat, Magnus Nordenskjöld, Christer Sundström, Gunilla Enblad, Riccardo Dalla-Favera, Huilai Zhang, Manuel R Teixeira, Laura Pasqualucci, Roujun Peng, Qiang Pan-Hammarström
Diffuse large B-cell lymphoma (DLBCL) is one of the most common and aggressive types of B-cell lymphoma. Deregulation of proto-oncogene expression after a translocation, most notably to the immunoglobulin heavy-chain locus (IGH), is one of the hallmarks of DLBCL. Using whole-genome sequencing analysis, we have identified the PD-L1/PD-L2 locus as a recurrent translocation partner for IGH in DLBCL. PIM1 and TP63 were also identified as novel translocation partners for PD-L1/PD-L2 Fluorescence in situ hybridization was furthermore used to rapidly screen an expanded DLBCL cohort...
June 16, 2016: Blood
https://www.readbyqxmd.com/read/24550227/genetic-lesions-associated-with-chronic-lymphocytic-leukemia-chemo-refractoriness
#2
Monica Messina, Ilaria Del Giudice, Hossein Khiabanian, Davide Rossi, Sabina Chiaretti, Silvia Rasi, Valeria Spina, Antony B Holmes, Marilisa Marinelli, Giulia Fabbri, Alfonso Piciocchi, Francesca R Mauro, Anna Guarini, Gianluca Gaidano, Riccardo Dalla-Favera, Laura Pasqualucci, Raul Rabadan, Robin Foà
Fludarabine refractoriness (FR) represents an unsolved clinical problem of chronic lymphocytic leukemia (CLL) management. Although next-generation sequencing studies have led to the identification of a number of genes frequently mutated in FR-CLL, a comprehensive evaluation of the FR-CLL genome has not been reported. Toward this end, we studied 10 FR-CLLs by combining whole-exome sequencing and copy number aberration (CNA) analysis, which showed an average of 16.3 somatic mutations and 4 CNAs per sample. Screening of recurrently mutated genes in 48 additional FR-CLLs revealed that ~70% of FR-CLLs carry ≥1 mutation in genes previously associated with CLL clinical course, including TP53 (27...
April 10, 2014: Blood
https://www.readbyqxmd.com/read/21282644/signatures-of-murine-b-cell-development-implicate-yy1-as-a-regulator-of-the-germinal-center-specific-program
#3
Michael R Green, Stefano Monti, Riccardo Dalla-Favera, Laura Pasqualucci, Nicole C Walsh, Marc Schmidt-Supprian, Jeffery L Kutok, Scott J Rodig, Donna S Neuberg, Klaus Rajewsky, Todd R Golub, Frederick W Alt, Margaret A Shipp, John P Manis
We utilized gene expression profiling of a comprehensive panel of purified developmentally defined normal murine B cells to identify unique transcriptional signatures for each subset. To elucidate transcription factor activities that function in a stage-specific fashion, we used gene sets that share transcription factor targets and found that germinal center B cells had a robust enrichment of up-regulated and down-regulated signatures compared with the other B-cell subsets. Notably, we found Yy1 and its targets to be central regulators of the germinal center B (GCB)-specific transcriptional program with binding of Yy1 to select signature genes in GCB cells, and translation of the Yy1 signatures to human GCB cells...
February 15, 2011: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/20829823/towards-patient-based-cancer-therapeutics
#4
Stuart L Schreiber, Alykhan F Shamji, Paul A Clemons, Cindy Hon, Angela N Koehler, Benito Munoz, Michelle Palmer, Andrew M Stern, Bridget K Wagner, Scott Powers, Scott W Lowe, Xuecui Guo, Alex Krasnitz, Eric T Sawey, Raffaella Sordella, Lincoln Stein, Lloyd C Trotman, Andrea Califano, Riccardo Dalla-Favera, Adolfo Ferrando, Antonio Iavarone, Laura Pasqualucci, José Silva, Brent R Stockwell, William C Hahn, Lynda Chin, Ronald A DePinho, Jesse S Boehm, Shuba Gopal, Alan Huang, David E Root, Barbara A Weir, Daniela S Gerhard, Jean Claude Zenklusen, Michael G Roth, Michael A White, John D Minna, John B MacMillan, Bruce A Posner
No abstract text is available yet for this article.
September 2010: Nature Biotechnology
https://www.readbyqxmd.com/read/17989719/gene-expression-profiling-suggests-primary-central-nervous-system-lymphomas-to-be-derived-from-a-late-germinal-center-b-cell
#5
M Montesinos-Rongen, A Brunn, S Bentink, K Basso, W K Lim, W Klapper, C Schaller, G Reifenberger, J Rubenstein, O D Wiestler, R Spang, R Dalla-Favera, R Siebert, M Deckert
To characterize the molecular origin of primary lymphomas of the central nervous system (PCNSL), 21 PCNSLs of immunocompetent patients were investigated by microarray-based gene expression profiling. Comparison of the transcriptional profile of PCNSL with various normal and neoplastic B-cell subsets demonstrated PCNSL (i) to display gene expression patterns most closely related to late germinal center B cells, (ii) to display a gene expression profile similar to systemic diffuse large B-cell lymphomas (DLBCLs) and (iii) to be in part assigned to the activated B-cell-like (ABC) or the germinal center B-cell-like (GCB) subtype of DLBCL...
February 2008: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/17828269/genotoxic-stress-regulates-expression-of-the-proto-oncogene-bcl6-in-germinal-center-b-cells
#6
Ryan T Phan, Masumichi Saito, Yukiko Kitagawa, Anthony R Means, Riccardo Dalla-Favera
Antigen-specific B cells are selected in germinal centers, the structure in which these cells proliferate while accomplishing genome-remodeling processes such as class-switch recombination and somatic hypermutation. These events are associated with considerable genotoxic stress, which cells tolerate through suppression of DNA-damage responses by Bcl-6, a transcription factor required for the formation of germinal centers. Here we show that the expression of Bcl-6 is regulated by DNA damage through a signaling pathway that promotes Bcl-6 degradation...
October 2007: Nature Immunology
https://www.readbyqxmd.com/read/17560272/the-role-of-activation-induced-deaminase-in-antibody-diversification-and-chromosome-translocations
#7
REVIEW
Almudena Ramiro, Bernardo Reina San-Martin, Kevin McBride, Mila Jankovic, Vasco Barreto, André Nussenzweig, Michel C Nussenzweig
Although B and T lymphocytes are similar in many respects including diversification of their antigen receptor genes by V(D)J recombination, 95% of all lymphomas diagnosed in the western world are of B-cell origin. Many of these are derived from mature B cells [Kuppers, R. (2005). Mechanisms of B-cell lymphoma pathogenesis. Nat. Rev. Cancer 5, 251-262] and display hallmark chromosome translocations involving immunoglobulin genes and a proto-oncogene partner whose expression becomes deregulated as a result of the translocation reaction [Kuppers, R...
2007: Advances in Immunology
https://www.readbyqxmd.com/read/16329192/new-insights-into-the-phenotype-and-cell-derivation-of-b-cell-chronic-lymphocytic-leukemia
#8
REVIEW
U Klein, R Dalla-Favera
For many decades, B cell chronic lymphocytic leukemia (B-CLL) stood out as a B cell-derived malignancy that was difficult to position within the framework of the available B cell differentiation scheme: First, the histology as well as the immunophenotype did not quite resemble that of any normal lymphocyte; second, in contrast to almost all other B cell tumor subtypes, the immunoglobulin variable region (IgV) genes of B-CLL cases could be either unmutated or somatically mutated; third, the genomic lesions observed in B-CLL were markedly distinct from those of the other major B cell malignancies, which typically exhibit balanced chromosome translocations...
2005: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/15870177/nfkappab-activity-function-and-target-gene-signatures-in-primary-mediastinal-large-b-cell-lymphoma-and-diffuse-large-b-cell-lymphoma-subtypes
#9
Friedrich Feuerhake, Jeffery L Kutok, Stefano Monti, Wen Chen, Ann S LaCasce, Giorgio Cattoretti, Paul Kurtin, Geraldine S Pinkus, Laurence de Leval, Nancy L Harris, Kerry J Savage, Donna Neuberg, Thomas M Habermann, Riccardo Dalla-Favera, Todd R Golub, Jon C Aster, Margaret A Shipp
Primary mediastinal large B-cell lymphoma (MLBCL) shares important clinical and molecular features with classic Hodgkin lymphoma, including nuclear localization of the nuclear factor kappaB (NFkappaB) subunit c-REL (reticuloendotheliosis viral oncogene homolog) in a pilot series. Herein, we analyzed c-REL subcellular localization in additional primary MLBCLs and characterized NFkappaB activity and function in a MLBCL cell line. The new primary MLBCLs had prominent c-REL nuclear staining, and the MLBCL cell line exhibited high levels of NFkappaB binding activity...
August 15, 2005: Blood
https://www.readbyqxmd.com/read/15550490/molecular-profiling-of-diffuse-large-b-cell-lymphoma-identifies-robust-subtypes-including-one-characterized-by-host-inflammatory-response
#10
Stefano Monti, Kerry J Savage, Jeffery L Kutok, Friedrich Feuerhake, Paul Kurtin, Martin Mihm, Bingyan Wu, Laura Pasqualucci, Donna Neuberg, Ricardo C T Aguiar, Paola Dal Cin, Christine Ladd, Geraldine S Pinkus, Gilles Salles, Nancy Lee Harris, Riccardo Dalla-Favera, Thomas M Habermann, Jon C Aster, Todd R Golub, Margaret A Shipp
Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease with recognized variability in clinical outcome, genetic features, and cells of origin. To date, transcriptional profiling has been used to highlight similarities between DLBCL tumor cells and normal B-cell subtypes and associate genes and pathways with unfavorable outcome. To identify robust and highly reproducible DL-BCL subtypes with comprehensive transcriptional signatures, we used a large series of newly diagnosed DLBCLs, whole genome arrays, and multiple clustering methods...
March 1, 2005: Blood
https://www.readbyqxmd.com/read/15507667/rt-pcr-analysis-of-rna-extracted-from-bouin-fixed-and-paraffin-embedded-lymphoid-tissues
#11
Annunziata Gloghini, Barbara Canal, Ulf Klein, Luigino Dal Maso, Tiziana Perin, Riccardo Dalla-Favera, Antonino Carbone
In the present study, we have investigated whether RNA can be efficiently isolated from Bouin-fixed or formalin-fixed, paraffin-embedded lymphoid tissue specimens. To this aim, we applied a new and simple method that includes the combination of proteinase K digestion and column purification. By this method, we demonstrated that the amplification of long fragments could be accomplished after a pre-heating step before cDNA synthesis associated with the use of enzymes that work at high temperature. By means of PCR using different primers for two examined genes (glyceraldehyde-3-phosphate dehydrogenase [GAPDH]- and CD40), we amplified segments of cDNA obtained by reverse transcription of the isolated RNA extracted from Bouin-fixed or formalin-fixed paraffin-embedded tissues...
November 2004: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/15304391/expression-of-the-aid-protein-in-normal-and-neoplastic-b-cells
#12
Laura Pasqualucci, Roberta Guglielmino, Jane Houldsworth, Jessica Mohr, Said Aoufouchi, Roberto Polakiewicz, R S K Chaganti, Riccardo Dalla-Favera
Somatic hypermutation (SHM) targets primarily the immunoglobulin variable region (IgV) genes in germinal center (GC) B cells, thereby allowing antibody affinity maturation. A malfunction of SHM, termed aberrant somatic hypermutation (ASHM), was found in about 50% of diffuse large B-cell lymphomas (DLBCLs), leading to mutations in the 5' sequences of multiple genes, including oncogenes. Although the SHM mechanism is largely unknown, it was shown to require the activation-induced cytidine deaminase (AID) gene...
November 15, 2004: Blood
https://www.readbyqxmd.com/read/14615382/relationship-between-rel-amplification-rel-function-and-clinical-and-biologic-features-in-diffuse-large-b-cell-lymphomas
#13
Jane Houldsworth, Adam B Olshen, Giorgio Cattoretti, Gerard B Donnelly, Julie Teruya-Feldstein, Jing Qin, Nallasivam Palanisamy, Yingjing Shen, Katerina Dyomina, Marina Petlakh, Qiulu Pan, Andrew D Zelenetz, Riccardo Dalla-Favera, R S K Chaganti
Although it has been suggested that REL is the critical target gene of 2p12-16 amplification in diffuse large B-cell lymphoma (DLBCL), little experimental evidence supports this notion. In the present study, we sought to evaluate the relationship between REL amplification and REL function in a panel of 46 newly diagnosed DLBCLs and to correlate with DLBCL subgroups as identified by gene expression profiles and clinical features. The results indicate that amplification of the REL locus is not associated with accumulation of the active form of REL, as evaluated by immunofluorescence analysis...
March 1, 2004: Blood
https://www.readbyqxmd.com/read/12933571/the-molecular-signature-of-mediastinal-large-b-cell-lymphoma-differs-from-that-of-other-diffuse-large-b-cell-lymphomas-and-shares-features-with-classical-hodgkin-lymphoma
#14
COMPARATIVE STUDY
Kerry J Savage, Stefano Monti, Jeffery L Kutok, Giorgio Cattoretti, Donna Neuberg, Laurence De Leval, Paul Kurtin, Paola Dal Cin, Christine Ladd, Friedrich Feuerhake, Ricardo C T Aguiar, Sigui Li, Gilles Salles, Francoise Berger, Wen Jing, Geraldine S Pinkus, Thomas Habermann, Riccardo Dalla-Favera, Nancy Lee Harris, Jon C Aster, Todd R Golub, Margaret A Shipp
Mediastinal large B-cell lymphoma (MLBCL) is a recently identified subtype of diffuse large B-cell lymphoma (DLBCL) that characteristically presents as localized tumors in young female patients. Although MLBCL has distinctive pathologic features, it clinically resembles the nodular sclerosis subtype of classical Hodgkin lymphoma (cHL). To elucidate the molecular features of MLBCL, we compared the gene expression profiles of newly diagnosed MLBCL and DLBCL and developed a classifier of these diseases. MLBCLs had low levels of expression of multiple components of the B-cell receptor signaling cascade, a profile resembling that of Reed-Sternberg cells of cHL...
December 1, 2003: Blood
https://www.readbyqxmd.com/read/12515714/mutations-of-the-bcl6-proto-oncogene-disrupt-its-negative-autoregulation-in-diffuse-large-b-cell-lymphoma
#15
Laura Pasqualucci, Anna Migliazza, Katia Basso, Jane Houldsworth, R S K Chaganti, Riccardo Dalla-Favera
The BCL6 proto-oncogene encodes a transcriptional repressor whose expression is deregulated by chromosomal translocations in approximately 40% of diffuse large B-cell lymphomas (DLBCLs). The BCL6 regulatory sequences are also targeted by somatic hypermutation in germinal center (GC) B cells and in a fraction of all GC-derived lymphomas. However, the functional consequences of these mutations are unknown. Here we report that a subset of mutations specifically associated with DLBCL causes deregulated BCL6 transcription...
April 15, 2003: Blood
https://www.readbyqxmd.com/read/12402037/acetylation-inactivates-the-transcriptional-repressor-bcl6
#16
Oksana R Bereshchenko, Wei Gu, Riccardo Dalla-Favera
The proto-oncogene BCL6 encodes a BTB/POZ-zinc finger transcriptional repressor that is necessary for germinal-center formation and has been implicated in the pathogenesis of B-cell lymphomas. Here we show that the co-activator p300 binds and acetylates BCL6 in vivo and inhibits its function. Acetylation disrupts the ability of BCL6 to recruit histone deacetylases (HDACs), thereby hindering its capacity to repress transcription and to induce cell transformation. BCL6 is acetylated under physiologic conditions in normal germinal-center B cells and in germinal center-derived B-cell tumors...
December 2002: Nature Genetics
https://www.readbyqxmd.com/read/12160729/bcl8-is-a-novel-evolutionarily-conserved-human-gene-family-encoding-proteins-with-presumptive-protein-kinase-a-anchoring-function
#17
Vadim G Dyomin, Seeta R Chaganti, Katerina Dyomina, Nallasivam Palanisamy, Vundavalli V V S Murty, Riccardo Dalla-Favera, R S K Chaganti
BCL8 is a novel human gene family initially identified through cloning of BCL8A, located at the t(14;15)(q32;q11-q13) translocation breakpoint, in a case of diffuse large B-cell lymphoma. Multiple copies of BCL8A map to the 1-Mb proximal duplicated region at 15q. We identified additional copies on human chromosomes 13 (BCL8B), 22 (BCL8C), 2 (BCL8D), and 10 (BCL8E) by cDNA cloning and sequence analysis. BCL8A, BCL8C, BCL8D, and BCL8E are truncated at the genomic level and are presumably pseudogenes or sterile transcripts...
August 2002: Genomics
https://www.readbyqxmd.com/read/12110671/c-myc-represses-and-miz-1-activates-the-murine-natural-resistance-associated-protein-1-promoter
#18
Holly Bowen, Thelma E Biggs, Emma Phillips, Stephen T Baker, V Hugh Perry, Derek A Mann, C Howard Barton
Iron is essential for growth, and impaired iron homoeostasis through a non-conserved mutation within murine Nramp1, also termed Slc11a1, contributes to susceptibility to infection. Nramp1 depletes the macrophage cytosol of iron, with effects on iron-regulated gene expression and iron-dependent processes. Wu and colleagues (Wu, K.-J., Polack, A., and Dalla-Favera, R. (1999) Science 283, 676-679) showed converse control of iron regulatory protein expression (IRP2) and H-ferritin by c-Myc, suggesting a role for c-Myc in enhancing cytoplasmic iron levels for growth...
September 20, 2002: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/11875462/tolerization-of-dendritic-cells-by-t-s-cells-the-crucial-role-of-inhibitory-receptors-ilt3-and-ilt4
#19
C C Chang, R Ciubotariu, J S Manavalan, J Yuan, A I Colovai, F Piazza, S Lederman, M Colonna, R Cortesini, R Dalla-Favera, N Suciu-Foca
Immunoglobulin-like transcript 3 (ILT3) and ILT4 belong to a family of inhibitory receptors expressed by human monocytes and dendritic cells. We show here that CD8+CD28(-) alloantigen-specific T suppressor (TS) cells induce the up-regulation of ILT3 and ILT4 on monocytes and dendritic cells, rendering these antigen-presenting cells (APCs) tolerogenic. Tolerogenic APCs show reduced expression of costimulatory molecules and induce antigen-specific unresponsiveness in CD4+ T helper cells. Studies of human heart transplant recipients showed that rejection-free patients have circulating TS cells, which induce the up-regulation of ILT3 and ILT4 in donor APCs...
March 2002: Nature Immunology
https://www.readbyqxmd.com/read/11733577/gene-expression-profiling-of-b-cell-chronic-lymphocytic-leukemia-reveals-a-homogeneous-phenotype-related-to-memory-b-cells
#20
U Klein, Y Tu, G A Stolovitzky, M Mattioli, G Cattoretti, H Husson, A Freedman, G Inghirami, L Cro, L Baldini, A Neri, A Califano, R Dalla-Favera
B cell-derived chronic lymphocytic leukemia (B-CLL) represents a common malignancy whose cell derivation and pathogenesis are unknown. Recent studies have shown that >50% of CLLs display hypermutated immunoglobulin variable region (IgV) sequences and a more favorable prognosis, suggesting that they may represent a distinct subset of CLLs which have transited through germinal centers (GCs), the physiologic site of IgV hypermutation. To further investigate the phenotype of CLLs, their cellular derivation and their relationship to normal B cells, we have analyzed their gene expression profiles using oligonucleotide-based DNA chip microarrays representative of approximately 12,000 genes...
December 3, 2001: Journal of Experimental Medicine
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