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https://www.readbyqxmd.com/read/29769262/a-new-molecular-assay-and-genomic-complexity-predict-outcome-in-conventional-and-leukemic-non-nodal-mantle-cell-lymphoma
#1
Guillem Clot, Pedro Jares, Eva Giné, Alba Navarro, Cristina Royo, Magda Pinyol, David Martín-Garcia, Santiago Demajo, Blanca Espinet, Antonio Salar, Ana Ferrer, Ana Muntañola, Marta Aymerich, Hilka Rauert-Wunderlich, Elaine S Jaffe, Joseph M Connors, Randy D Gascoyne, Jan Delabie, Armando López-Guillermo, German Ott, George W Wright, Louis M Staudt, Andreas Rosenwald, David W Scott, Lisa M Rimsza, Sílvia Beà, Elías Campo
Mantle cell lymphoma (MCL) is an aggressive B-cell malignancy but some patients have a very indolent evolution. This heterogeneous course is related, in part, to the different biological characteristics of conventional MCL (cMCL) and the distinct subgroup of leukemic non-nodal MCL (nnMCL). Robust criteria to distinguish these MCL subtypes and additional biological parameters that influence their evolution are not well defined. Herein, we describe a novel molecular assay that reliably distinguishes cMCL and nnMCL using blood samples...
May 16, 2018: Blood
https://www.readbyqxmd.com/read/29730836/round-robin-test-for-the-cell-of-origin-classification-of-diffuse-large-b-cell-lymphoma-a-feasibility-study-using-full-slide-staining
#2
Sarah Reinke, Julia Richter, Falko Fend, Alfred Feller, Martin-Leo Hansmann, Katrin Hüttl, Ilske Oschlies, German Ott, Peter Möller, Andreas Rosenwald, Harald Stein, Michael Altenbuchinger, Rainer Spang, Wolfram Klapper
Diffuse large B-cell lymphoma (DLBCL) is subdivided by gene expression analysis (GEP) into two molecular subtypes named germinal center B-cell-like (GCB) and activated B-cell-like (ABC) after their putative cell-of-origin (COO). Determination of the COO is considered mandatory in any new-diagnosed DLBCL, not otherwise specified according to the updated WHO classification. Despite the fact that pathologists are free to choose the method for COO classification, immunohistochemical (IHC) assays are most widely used...
May 5, 2018: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/29713087/molecular-subtypes-of-diffuse-large-b-cell-lymphoma-are-associated-with-distinct-pathogenic-mechanisms-and-outcomes
#3
Bjoern Chapuy, Chip Stewart, Andrew J Dunford, Jaegil Kim, Atanas Kamburov, Robert A Redd, Mike S Lawrence, Margaretha G M Roemer, Amy J Li, Marita Ziepert, Annette M Staiger, Jeremiah A Wala, Matthew D Ducar, Ignaty Leshchiner, Ester Rheinbay, Amaro Taylor-Weiner, Caroline A Coughlin, Julian M Hess, Chandra S Pedamallu, Dimitri Livitz, Daniel Rosebrock, Mara Rosenberg, Adam A Tracy, Heike Horn, Paul van Hummelen, Andrew L Feldman, Brian K Link, Anne J Novak, James R Cerhan, Thomas M Habermann, Reiner Siebert, Andreas Rosenwald, Aaron R Thorner, Matthew L Meyerson, Todd R Golub, Rameen Beroukhim, Gerald G Wulf, German Ott, Scott J Rodig, Stefano Monti, Donna S Neuberg, Markus Loeffler, Michael Pfreundschuh, Lorenz Trümper, Gad Getz, Margaret A Shipp
Diffuse large B cell lymphoma (DLBCL), the most common lymphoid malignancy in adults, is a clinically and genetically heterogeneous disease that is further classified into transcriptionally defined activated B cell (ABC) and germinal center B cell (GCB) subtypes. We carried out a comprehensive genetic analysis of 304 primary DLBCLs and identified low-frequency alterations, captured recurrent mutations, somatic copy number alterations, and structural variants, and defined coordinate signatures in patients with available outcome data...
April 30, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29666909/-aggressive-b%C3%A2-cell-lymphomas-recommendations-from-the-german-panel-of-reference-pathologists-in-the-competence-network-on-malignant-lymphomas-on-diagnostic-procedures-according-to-the-current-who-classification-update-2017
#4
REVIEW
W Klapper, F Fend, A Feller, M L Hansmann, P Möller, H Stein, A Rosenwald, G Ott
The update of the 4th edition of the WHO classification for hematopoietic neoplasms introduces changes in the field of mature aggressive B‑cell lymphomas that are relevant to diagnostic pathologists. In daily practice, the question arises of which analysis should be performed when diagnosing the most common lymphoma entity, diffuse large B‑cell lymphoma. We discuss the importance of the cell of origin, the analysis of MYC translocations, and the delineation of the new WHO entities of high-grade B‑cell lymphomas...
April 17, 2018: Der Pathologe
https://www.readbyqxmd.com/read/29575428/identification-of-candida-albicans-regulatory-genes-governing-mucosal-infection
#5
Juliane Meir, Elena Hartmann, Marie-Therese Eckstein, Eva Guiducci, Florian Kirchner, Andreas Rosenwald, Salomé LeibundGut-Landmann, J Christian Pérez
The fungus Candida albicans thrives on a variety of human mucosae, yet the fungal determinants that contribute to fitness on these surfaces remain underexplored. Here, by screening a collection of C. albicans deletion strains in a mouse model of oral infection (oropharyngeal candidiasis), we identify several novel regulatory genes that modulate the fitness of the fungus in this locale. We investigate in detail the interplay between the host mucosa and one of the identified mutants and establish that the C...
March 25, 2018: Cellular Microbiology
https://www.readbyqxmd.com/read/29567771/gene-expression-profiling-reveals-a-close-relationship-between-follicular-lymphoma-grade-3a-and-3b-but-distinct-profiles-of-follicular-lymphoma-grade-1-and-2
#6
Heike Horn, Christian Kohler, Raphael Witzig, Markus Kreuz, Ellen Leich, Wolfram Klapper, Michael Hummel, Markus Loeffler, Lorenz Trümper, Rainer Spang, Andreas Rosenwald, German Ott
A linear progression model of follicular lymphomas (FL) FL1, FL2 and FL3A has been favored, since FL 3A often coexist with a FL1/2 component. FL3B, in contrast, is thought to be more closely related to diffuse large B-cell lymphoma (DLBCL), and both FL3B and DLBCL are often simultaneously present in one tumor (DLBCL/FL3B). To obtain more detailed insights into FL progression, comprehensive analysis of a well-defined set of FL1/2 (n=22), FL3A (n=16), FL3B (n=6), DLBCL/FL3B (n=9) and germincal center B-cell(GCB)-type DLBCL (n=45) was performed using gene expression profiling, immunohistochemical staining and genetic analysis by fluorescence in situ hybridization (FISH)...
March 22, 2018: Haematologica
https://www.readbyqxmd.com/read/29481902/panel-sequencing-shows-recurrent-genetic-fas-alterations-in-primary-cutaneous-marginal-zone-lymphoma
#7
Katja Maurus, Silke Appenzeller, Sabine Roth, Jochen Kuper, Simone Rost, Svenja Meierjohann, Panagiota Arampatzi, Matthias Goebeler, Andreas Rosenwald, Eva Geissinger, Marion Wobser
Primary cutaneous marginal zone lymphoma (PCMZL) represents an indolent subtype of non-Hodgkin lymphoma that is clinically characterized by slowly growing skin tumors with a very low propensity for systemic dissemination. The underlying genetic basis of PCMZL has not been comprehensively elucidated. To gain deeper insight into the molecular pathogenesis of PCMZL, we performed hybridization-based panel sequencing of 38 patients with well-characterized PCMZL. In 32 of the 38 patients, we identified genetic alterations within 39 selected target genes...
February 23, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29475959/high-grade-b-cell-lymphoma-with-myc-and-bcl2-and-or-bcl6-rearrangements-with-diffuse-large-b-cell-lymphoma-morphology
#8
David W Scott, Rebecca L King, Annette M Staiger, Susana Ben-Neriah, Aixiang Jiang, Heike Horn, Anja Mottok, Pedro Farinha, Graham W Slack, Daisuke Ennishi, Norbert Schmitz, Michael Pfreundschuh, Grzegorz S Nowakowski, Brad S Kahl, Joseph M Connors, Randy D Gascoyne, German Ott, William R Macon, Andreas Rosenwald
High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (HGBL-DH/TH) is a newly defined entity in the latest World Health Organization Classification. Accurate diagnosis would appear to mandate fluorescence in situ hybridization (FISH) for all tumors with diffuse large B-cell lymphoma (DLBCL) morphology. We present the results of FISH, cell-of-origin, and immunohistochemistry (IHC) testing from 1228 DLBCL biopsies from 3 clinical trials and a population-based registry. HGBL-DH/TH made up 7.9% of the DLBCL, confined primarily to the germinal center B-cell-like (GCB; 13...
May 3, 2018: Blood
https://www.readbyqxmd.com/read/29390004/the-development-and-application-of-bioinformatics-core-competencies-to-improve-bioinformatics-training-and-education
#9
Nicola Mulder, Russell Schwartz, Michelle D Brazas, Cath Brooksbank, Bruno Gaeta, Sarah L Morgan, Mark A Pauley, Anne Rosenwald, Gabriella Rustici, Michael Sierk, Tandy Warnow, Lonnie Welch
Bioinformatics is recognized as part of the essential knowledge base of numerous career paths in biomedical research and healthcare. However, there is little agreement in the field over what that knowledge entails or how best to provide it. These disagreements are compounded by the wide range of populations in need of bioinformatics training, with divergent prior backgrounds and intended application areas. The Curriculum Task Force of the International Society of Computational Biology (ISCB) Education Committee has sought to provide a framework for training needs and curricula in terms of a set of bioinformatics core competencies that cut across many user personas and training programs...
February 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29367645/cd40l-mediated-alternative-nf%C3%AE%C2%BAb-signaling-induces-resistance-to-bcr-inhibitors-in-patients-with-mantle-cell-lymphoma
#10
Hilka Rauert-Wunderlich, Martina Rudelius, Ingolf Berberich, Andreas Rosenwald
Drug resistance is a significant obstacle in cancer treatment and therefore a frequent subject of research. Developed or primary resistance limits the treatment success of inhibitors of the B cell receptor (BCR) pathway in mantle cell lymphoma (MCL) patients. Recent research has highlighted the role of the nuclear factor-kappa B (NFκB) pathway in the context of resistance to BCR inhibitors in MCL. In this study, we analyzed the dependency of MCL cell lines on NFκB signaling and illustrated the ability of CD40L to activate the alternative NFκB pathway in MCL...
January 24, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29355824/next-generation-sequencing-for-lymphomas-perfecting-a-pipeline-for-personalized-pathobiologic-and-prognostic-predictions
#11
Robert S Ohgami, Andreas Rosenwald, Adam Bagg
This commentary highlights the article by Hung et al that details the design and implementation of a 32-gene next-generation sequencing panel for lymphomas and compares hybrid-capture with amplicon-based next-generation sequencing approaches.
March 2018: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/29346772/peroxisome-proliferator-activated-receptor-gamma-controls-mature-brown-adipocyte-inducibility-through-glycerol-kinase
#12
David Lasar, Matthias Rosenwald, Elke Kiehlmann, Miroslav Balaz, Bettina Tall, Lennart Opitz, Martin E Lidell, Nicola Zamboni, Petra Krznar, Wenfei Sun, Lukas Varga, Patrik Stefanicka, Jozef Ukropec, Pirjo Nuutila, Kirsi Virtanen, Ez-Zoubir Amri, Sven Enerbäck, Walter Wahli, Christian Wolfrum
Peroxisome proliferator-activated receptors (PPARs) have been suggested as the master regulators of adipose tissue formation. However, their role in regulating brown fat functionality has not been resolved. To address this question, we generated mice with inducible brown fat-specific deletions of PPARα, β/δ, and γ, respectively. We found that both PPARα and β/δδ are dispensable for brown fat function. In contrast, we could show that ablation of PPARγ in vitro and in vivo led to a reduced thermogenic capacity accompanied by a loss of inducibility by β-adrenergic signaling, as well as a shift from oxidative fatty acid metabolism to glucose utilization...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29232438/refractory-or-relapsed-aggressive-b-cell-lymphoma-failing-r-chop-an-analysis-of-patients-treated-on-the-ricover-60-trial
#13
B Glass, A J Dohm, L H Truemper, M Pfreundschuh, A Bleckmann, G G Wulf, A Rosenwald, M Ziepert, N Schmitz
Background: The prognosis of elderly patients with aggressive B-non-Hodgkin's lymphoma after first lymphoma-related treatment failure (TF-L) is not well described. Methods: We analysed patient characteristics including the presence of MYC rearrangements and MYC-expression immunohistochemistry (IHC) at diagnosis and modalities of salvage therapy and their impact on the prognosis of patients between 61 and 80 years who had been treated on the RICOVER-60 trial. Results: TF-L occurred in 301 of the 1222 (24...
December 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29228566/targeting-cxcr4-with-68-ga-pentixafor-a-suitable-theranostic-approach-in-pleural-mesothelioma
#14
Constantin Lapa, Stefan Kircher, Andreas Schirbel, Andreas Rosenwald, Saskia Kropf, Theo Pelzer, Thorsten Walles, Andreas K Buck, Wolfgang A Weber, Hans-Juergen Wester, Ken Herrmann, Katharina Lückerath
C-X-C motif chemokine receptor 4 (CXCR4) is a key factor for tumor growth and metastasis in several types of human cancer. This study investigated the feasibility of CXCR4-directed imaging with positron emission tomography/computed tomography (PET/CT) using [68 Ga]Pentixafor in malignant pleural mesothelioma. Six patients with pleural mesothelioma underwent [68 Ga]Pentixafor-PET/CT. 2'-[18 F]fluoro-2'-deoxy-D-glucose ([18 F]FDG)-PET/CT (4/6 patients) and immunohistochemistry obtained from biopsy or surgery (all) served as standards of reference...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29196411/expression-of-tp53-is-associated-with-the-outcome-of-mcl-independent-of-mipi-and-ki-67-in-trials-of-the-european-mcl-network
#15
Sietse M Aukema, Eva Hoster, Andreas Rosenwald, Danielle Canoni, Marie-Hélène Delfau-Larue, Grzegorz Rymkiewicz, Christoph Thorns, Sylvia Hartmann, Hanneke Kluin-Nelemans, Olivier Hermine, Martin Dreyling, Wolfram Klapper
Currently, prediction of time to treatment failure (TTF) and overall survival (OS) in mantle cell lymphoma (MCL) is based on the clinical factors included in the Mantle Cell Lymphoma International Prognostic Index (MIPI), and proliferation is assessed by Ki67. However, TP53 and SOX11 immunohistochemistry might improve risk stratification. We performed SOX11 and TP53 immunohistochemistry on the so far largest published cohort of lymphoma specimens (n = 365). All patients were treated in prospective trials of the European MCL Network...
January 25, 2018: Blood
https://www.readbyqxmd.com/read/29193015/the-exomic-landscape-of-t-14-18-negative-diffuse-follicular-lymphoma-with-1p36-deletion
#16
Alberto Zamò, Jordan Pischimarov, Heike Horn, German Ott, Andreas Rosenwald, Ellen Leich
Predominantly diffuse t(14;18) negative follicular lymphoma (FL) with 1p36 deletion shows distinctive clinical, morphological and molecular features that distinguish it from classical FL. In order to investigate whether it possesses a unique mutation profile, we performed whole exome sequencing of six well-characterised cases. Our analysis showed that the mutational landscape of this subtype is largely distinct from classical FL. It appears to harbour several recurrent mutations, affecting STAT6, CREBBP and basal membrane protein genes with high frequency...
February 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29187510/ercc1-as-predictive-biomarker-to-platinum-based-chemotherapy-in-adrenocortical-carcinomas
#17
Valeria Laufs, Barbara Altieri, Silviu Sbiera, Stefan Kircher, Sonja Steinhauer, Felix Beuschlein, Marcus Quinkler, Holger S Willenberg, Andreas Rosenwald, Martin Fassnacht, Cristina L Ronchi
OBJECTIVE: Platinum-based chemotherapy (PBC) is the most effective cytotoxic treatment for advanced adrenocortical carcinoma (ACC). Excision repair cross complementing group 1 (ERCC1) plays a critical role in the repair of platinum-induced DNA damage. Two studies investigating the role of ERCC1 immunostaining as a predictive marker for the response to PBC in ACC had reported conflicting results. Both studies used the ERCC1-antibody clone 8F1 that later turned out to be not specific. The aim of this study was to evaluate the predictive role of ERCC1 with a new specific antibody in a larger series of ACC...
February 2018: European Journal of Endocrinology
https://www.readbyqxmd.com/read/29122756/foxp1-expression-is-a-prognostic-biomarker-in-follicular-lymphoma-treated-with-rituximab-and-chemotherapy
#18
Anja Mottok, Vindi Jurinovic, Pedro Farinha, Andreas Rosenwald, Ellen Leich, German Ott, Heike Horn, Wolfram Klapper, Michael Boesl, Wolfgang Hiddemann, Christian Steidl, Joseph M Connors, Laurie H Sehn, Randy D Gascoyne, Eva Hoster, Oliver Weigert, Robert Kridel
Follicular lymphoma (FL) is a clinically and molecularly highly heterogeneous disease, yet prognostication relies predominantly on clinical tools. We recently demonstrated that integration of mutation status of 7 genes, including EZH2 and MEF2B, improves risk stratification. We mined gene expression data to uncover genes that are differentially expressed in EZH2 - and MEF2B -mutated cases. We focused on FOXP1 and assessed its protein expression by immunohistochemistry (IHC) in 763 tissue biopsies. For outcome correlation, a population-based training cohort of 142 patients with FL treated with rituximab, cyclophosphamide, vincristine, and prednisone, and a clinical trial validation cohort comprising 395 patients treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) ± rituximab were used...
January 11, 2018: Blood
https://www.readbyqxmd.com/read/29092062/gemcitabine-based-chemotherapy-in-adrenocortical-carcinoma-a-multicenter-study-of-efficacy-and-predictive-factors
#19
MULTICENTER STUDY
Judith E K Henning, Timo Deutschbein, Barbara Altieri, Sonja Steinhauer, Stefan Kircher, Silviu Sbiera, Vanessa Wild, Wiebke Schlötelburg, Matthias Kroiss, Paola Perotti, Andreas Rosenwald, Alfredo Berruti, Martin Fassnacht, Cristina L Ronchi
Context: Adrenocortical carcinoma (ACC) is rare and confers an unfavorable prognosis in advanced stages. Other than combination chemotherapy with cisplatin, etoposide, doxorubicin, and mitotane, the second- and third-line regimens are not well-established. Gemcitabine (GEM)-based chemotherapy was suggested in a phase 2 clinical trial with 28 patients. In other solid tumors, human equilibrative nucleoside transporter type 1 (hENT1) and/or ribonucleotide reductase catalytic subunit M1 (RRM1) expression have been associated with resistance to GEM...
November 1, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29079592/inhibition-of-focal-adhesion-kinase-overcomes-resistance-of-mantle-cell-lymphoma-to-ibrutinib-in-the-bone-marrow-microenvironment
#20
Martina Rudelius, Mathias Tillmann Rosenfeldt, Ellen Leich, Hilka Rauert-Wunderlich, Antonio Giovanni Solimando, Andreas Beilhack, German Ott, Andreas Rosenwald
Mantle cell lymphoma and other lymphoma subtypes often spread to the bone marrow, and stromal interactions mediated by focal adhesion kinase frequently enhance survival and drug resistance of the lymphoma cells. To study the role of focal adhesion kinase in mantle cell lymphoma, immunohistochemistry of primary cases and functional analysis of mantle cell lymphoma cell lines and primary mantle cell lymphoma cells co-cultured with bone marrow stromal cells (BMSC) using small molecule inhibitors and RNAi-based focal adhesion kinase silencing was performed...
January 2018: Haematologica
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