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1. Transcriptional reprogramming by mutated IRF4 in lymphoma

Author

Schleussner, Nikolai, Cauchy, Pierre, Franke, Vedran, Giefing, Maciej, Fornes, Oriol, Vankadari, Naveen, Assi, Salam A., Costanza, Mariantonia, Weniger, Marc A., Akalin, Altuna, Anagnostopoulos, Ioannis, Bukur, Thomas, Casarotto, Marco G., Damm, Frederik, Daumke, Oliver, Edginton-White, Benjamin, Gebhardt, J. Christof M., Grau, Michael, Grunwald, Stephan, Hansmann, Martin-Leo, Hartmann, Sylvia, Huber, Lionel, Kärgel, Eva, Lusatis, Simone, Noerenberg, Daniel, Obier, Nadine, Pannicke, Ulrich, Fischer, Anja, Reisser, Anja, Rosenwald, Andreas, Schwarz, Klaus, Sundararaj, Srinivasan, Weilemann, Andre, Winkler, Wiebke, Xu, Wendan, Lenz, Georg, Rajewsky, Klaus, Wasserman, Wyeth W., Cockerill, Peter N., Scheidereit, Claus, Siebert, Reiner, Küppers, Ralf, Grosschedl, Rudolf, Janz, Martin, Bonifer, Constanze, and Mathas, Stephan

Published
2023
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4. Imaging bridges pathology and radiology

Author

Hansmann, Martin-Leo, Klauschen, Frederick, Samek, Wojciech, Müller, Klaus-Robert, Donnadieu, Emmanuel, Scharf, Sonja, Hartmann, Sylvia, Koch, Ina, Ackermann, Jörg, Pantanowitz, Liron, Schäfer, Hendrik, and Wurzel, Patrick

Published
2023
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5. Checkpoint inhibition enhances cell contacts between CD4+ T cells and Hodgkin-Reed-Sternberg cells of classic Hodgkin lymphoma

Author

Yadigaroglu, Kübra, primary, Scharf, Sonja, additional, Gretser, Steffen, additional, Schäfer, Hendrik, additional, Deli, Aresu Sadeghi Shoreh, additional, Loth, Andreas G., additional, Yegoryan, Hasmik, additional, Schmitz, Roland, additional, Donnadieu, Emmanuel, additional, Hansmann, Martin-Leo, additional, and Hartmann, Sylvia, additional

Published
2024
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8. Automated Image Analysis of Hodgkin lymphoma

Author

Schmitz, Alexander, Schäfer, Tim, Schäfer, Hendrik, Döring, Claudia, Ackermann, Jörg, Dichter, Norbert, Hartmann, Sylvia, Hansmann, Martin-Leo, and Koch, Ina

Subjects
Quantitative Biology - Tissues and Organs, Physics - Medical Physics, Quantitative Biology - Cell Behavior
Abstract

Hodgkin lymphoma is an unusual type of lymphoma, arising from malignant B-cells. Morphological and immunohistochemical features of malignant cells and their distribution differ from other cancer types. Based on systematic tissue image analysis, computer-aided exploration can provide new insights into Hodgkin lymphoma pathology. In this paper, we report results from an image analysis of CD30 immunostained Hodgkin lymphoma tissue section images. To the best of our knowledge, this is the first systematic application of image analysis to a set of tissue sections of Hodgkin lymphoma. We have implemented an automatic procedure to handle and explore image data in Aperio's SVS format. We use pre-processing approaches on a down-scaled image to separate the image objects from the background. Then, we apply a supervised classification method to assign pixels to predefined classes. Our pre-processing method is able to separate the tissue content of images from the image background. We analyzed three immunohistologically defined groups, non-lymphoma and the two most common forms of Hodgkin lymphoma, nodular sclerosis and mixed cellularity type. We found that nodular sclerosis and non-lymphoma images exhibit different amounts of CD30 stain, whereas mixed cellularity type exhibits a large variance and overlaps with the other groups. The results can be seen as a first step to computationally identify tumor regions in the images. This allows us to focus on these regions when performing computationally expensive tasks like object detection in the high-resolution image., Comment: 12 papes, 5 figures, Dagstuhl seminar, Dagstuhl Seminar 12291 "Structure Discovery in Biology: Motifs, Networks & Phylogenies"

Published
2012

9. Hyper-N-glycosylated SAMD14 and neurabin-I as driver autoantigens of primary central nervous system lymphoma

Author

Thurner, Lorenz, Preuss, Klaus-Dieter, Bewarder, Moritz, Kemele, Maria, Fadle, Natalie, Regitz, Evi, Altmeyer, Sarah, Schormann, Claudia, Poeschel, Viola, Ziepert, Marita, Walter, Silke, Roth, Patrick, Weller, Michael, Szczepanowski, Monika, Klapper, Wolfram, Monoranu, Camelia, Rosenwald, Andreas, Möller, Peter, Hartmann, Sylvia, Hansmann, Martin-Leo, Mackensen, Andreas, Schäfer, Henning, Schorb, Elisabeth, Illerhaus, Gerald, Buslei, Rolf, Bohle, Rainer Maria, Stilgenbauer, Stephan, Kim, Yoo-Jin, and Pfreundschuh, Michael

Published
2018
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10. Duodenal-type and nodal follicular lymphomas differ by their immune microenvironment rather than their mutation profiles

Author

Hellmuth, Johannes C., Louissaint, Abner, Jr, Szczepanowski, Monika, Haebe, Sarah, Pastore, Alessandro, Alig, Stefan, Staiger, Annette M., Hartmann, Sylvia, Kridel, Robert, Ducar, Matthew D., Koch, Peter, Dreyling, Martin, Hansmann, Martin-Leo, Ott, German, Rosenwald, Andreas, Gascoyne, Randy D., Weinstock, David M., Hiddemann, Wolfgang, Klapper, Wolfram, and Weigert, Oliver

Published
2018
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12. LRPAP1 is a frequent proliferation-inducing antigen of BCRs of mantle cell lymphomas and can be used for specific therapeutic targeting

Author

Thurner, Lorenz, Hartmann, Sylvia, Fadle, Natalie, Kemele, Maria, Bock, Theresa, Bewarder, Moritz, Regitz, Evi, Neumann, Frank, Nimmesgern, Anna, von Müller, Lutz, Pott, Christiane, Kim, Yoo-Jin, Bohle, Rainer Maria, Wasik, Mariusz, Schuster, Stephen J., Hansmann, Martin-Leo, Preuss, Klaus-Dieter, and Pfreundschuh, Michael

Published
2019
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14. The RHOA Mutation G17V Does Not Lead to Increased Migration of Human Malignant T Cells but Is Associated with Matrix Remodelling

Author

Merk-Ahmad, Katrin, primary, Bein, Julia, additional, Scharf, Sonja, additional, Schäfer, Hendrik, additional, Bexte, Tobias, additional, Ullrich, Evelyn, additional, Loth, Andreas G., additional, Flinner, Nadine, additional, Senff, Tina, additional, Schneider, Olga, additional, Hansmann, Martin-Leo, additional, Piel, Matthieu, additional, Häupl, Björn, additional, Oellerich, Thomas, additional, Donnadieu, Emmanuel, additional, and Hartmann, Sylvia, additional

Published
2023
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15. B-cell receptor reactivity against Rothia mucilaginosa in nodular lymphocyte-predominant Hodgkin lymphoma

Author

Thurner, Lorenz, primary, Fadle, Natalie, additional, Regitz, Evi, additional, Roth, Sophie, additional, Cetin, Onur, additional, Kos, Igor Age, additional, Hess, Simon Mauro, additional, Bein, Julia, additional, Bohle, Rainer Maria, additional, Vornanen, Martine, additional, Sundström, Christer, additional, De Leval, Laurence, additional, Tiacci, Enrico, additional, Borchmann, Peter, additional, Engert, Andreas, additional, Poeschel, Viola, additional, Held, Gerhard, additional, Schwarz, Eva C., additional, Neumann, Frank, additional, Preuss, Klaus-Dieter, additional, Hoth, Markus, additional, Küppers, Ralf, additional, Lehman, Karola, additional, Hansmann, Martin-Leo, additional, Becker, Sören L., additional, Bewarder, Moritz, additional, and Hartmann, Sylvia, additional

Published
2023
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17. B-cell receptor reactivity against Rothia mucilaginosa in nodular lymphocyte-predominant Hodgkin lymphoma

Author

Thurner, Lorenz, Fadle, Natalie, Regitz, Evi, Roth, Sophie, Cetin, Onur, Kos, Igor Age, Hess, Simon Mauro, Bein, Julia, Bohle, Rainer Maria, Vornanen, Martine, Sundström, Christer, de Leval, Laurence, Tiacci, Enrico, Borchmann, Peter, Engert, Andreas, Poeschel, Viola, Held, Gerhard, Schwarz, Eva C., Neumann, Frank, Preuss, Klaus -Dieter, Hoth, Markus, Kueppers, Ralf, Lehmann, Karola, Hansmann, Martin-Leo, Becker, Soeren L., Bewarder, Moritz, Hartmann, Sylvia, Thurner, Lorenz, Fadle, Natalie, Regitz, Evi, Roth, Sophie, Cetin, Onur, Kos, Igor Age, Hess, Simon Mauro, Bein, Julia, Bohle, Rainer Maria, Vornanen, Martine, Sundström, Christer, de Leval, Laurence, Tiacci, Enrico, Borchmann, Peter, Engert, Andreas, Poeschel, Viola, Held, Gerhard, Schwarz, Eva C., Neumann, Frank, Preuss, Klaus -Dieter, Hoth, Markus, Kueppers, Ralf, Lehmann, Karola, Hansmann, Martin-Leo, Becker, Soeren L., Bewarder, Moritz, and Hartmann, Sylvia

Abstract

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a Hodgkin lymphoma expressing functional B-cell receptors (BCR). Recently, we described a dual stimulation model of IgD+ lymphocyte-predominant cells by Moraxella catarrhalis antigen RpoC and its superantigen MID/hag, associated with extralong CDR3 and HLA-DRB1*04 or HLA-DRB1*07 haplotype. The aim of the present study was to extend the antigen screening to further bacteria and viruses. The fragment antibody-binding (Fab) regions of seven new and 15 previously reported cases were analyzed. The reactivity of non-Moraxella spp.-reactive Fab regions against lysates of Rothia mucilaginosa was observed in 5/22 (22.7%) cases. Galactofuranosyl transferase (Gltf) and 2,3-butanediol dehydrogenase (Bdh) of R. mucilaginosa were identified by comparative silver-and immuno-staining in two-dimensional gels, with subsequent mass spectrometry and validation by western blots and enzyme-linked immunosorbent assay. Both R. mucilaginosa Gltf and Bdh induced BCR pathway activation and proliferation in vitro. Apoptosis was induced by recombinant Gltf/ETA'-immunotoxin conjugates in DEV cells expressing recombinant R. mucilaginosa-reactive BCR. Reactivity against M. catarrhalis RpoC was confirmed in 3/7 newly expressed BCR (total 10/22 reactive to Moraxella spp.), resulting in 15/22 (68.2%) cases with BCR reactivity against defined bacterial antigens. These findings strengthen the hypothesis of bacterial trigger contributing to subsets of NLPHL.

Published
2023
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18. Lymphocyte predominant cells detect Moraxella catarrhalis-derived antigens in nodular lymphocyte-predominant Hodgkin lymphoma

Author

Thurner, Lorenz, Hartmann, Sylvia, Fadle, Natalie, Regitz, Evi, Kemele, Maria, Kim, Yoo-Jin, Bohle, Rainer Maria, Nimmesgern, Anna, von Müller, Lutz, Kempf, Volkhard A. J., Weniger, Marc A., Neumann, Frank, Schneider, Nadine, Vornanen, Martine, Sundström, Christer, de Leval, Laurence, Engert, Andreas, Eichenauer, Dennis A., Küppers, Ralf, Preuss, Klaus-Dieter, Hansmann, Martin-Leo, and Pfreundschuh, Michael

Published
2020
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19. Human [CD30.sup.+] B cells represent a unique subset related to Hodgkin lymphoma cells

Author

Weniger, Marc A., Tiacci, Enrico, Schneider, Stefanie, Arnolds, Judith, Ruschenbaum, Sabrina, Duppach, Janine, Seifert, Marc, Doring, Claudia, Hansmann, Martin-Leo, and Kuppers, Ralf

Subjects
Gene expression -- Research, Lymph nodes -- Research -- Physiological aspects, B cells -- Research -- Physiological aspects, Hodgkin's disease -- Research -- Risk factors -- Genetic aspects, Membrane proteins -- Research -- Physiological aspects, Health care industry
Abstract

Very few B cells in germinal centers (GCs) and extrafollicular (EF) regions of lymph nodes express CD30. Their specific features and relationship to [CD30.sup.-]expressing Hodgkin and Reed/Sternberg (HRS) cells of Hodgkin lymphoma are unclear but highly relevant, because numerous patients with lymphoma are currently treated with an anti-CD30 immunotoxin. We performed a comprehensive analysis of human [CD30.sup.+] B cells. Phenotypic and IgV gene analyses indicated that [CD30.sup.+] GC B lymphocytes represent typical GC B cells, and that [CD30.sup.+] EF B cells are mostly post-GC B cells. The transcriptomes of [CD30.sup.+] GC and EF B cells largely overlapped, sharing a strong MYC signature, but were strikingly different from conventional GC B cells and memory B and plasma cells, respectively. [CD30.sup.+] GC B cells represent [MYC.sup.+] centrocytes redifferentiating into centroblasts; [CD30.sup.+] EF B cells represent active, proliferating memory B cells. HRS cells shared typical transcriptome patterns with [CD30.sup.+] B cells, suggesting that they originate from these lymphocytes or acquire their characteristic features during lymphomagenesis. By comparing HRS to normal [CD30.sup.+] B cells we redefined aberrant and disease-specific features of HRS cells. A remarkable downregulation of genes regulating genomic stability and cytokinesis in HRS cells may explain their genomic instability and multinuclearity., Introduction CD30 (TNFRSF8) is a transmembrane glycosylated protein and member of the tumor necrosis factor receptor superfamily (1). Within the hematopoietic system, this receptor is expressed by only a few [...]

Published
2018
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22. Identification of two unannotated miRNAs in classic Hodgkin lymphoma cell lines

Author

Ustaszewski, Adam, primary, Paczkowska, Julia, additional, Janiszewska, Joanna, additional, Bernhart, Stephan H., additional, Bein, Julia, additional, Russiñol, Núria, additional, Hansmann, Martin-Leo, additional, Chapaprieta, Vicente, additional, Martín-Subero, José I., additional, Siebert, Reiner, additional, Hartmann, Sylvia, additional, and Giefing, Maciej, additional

Published
2023
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24. Rare Occurrence of Classical Hodgkin's Disease as a T Cell Lymphoma

Author

Müschen, Markus, Rajewsky, Klaus, Bräuninger, Andreas, Baur, Audrey Sylvia, Oudejans, Joost J, Roers, Axel, Hansmann, Martin-Leo, and Küppers, Ralf

Subjects
Genetics, Rare Diseases, Cancer, Lymphoma, Hematology, 2.1 Biological and endogenous factors, Aetiology, Adult, Base Sequence, Hodgkin Disease, Humans, Lymphoma, T-Cell, Male, Middle Aged, Molecular Sequence Data, Reed-Sternberg Cells, Hodgkin's disease, T cell receptor genes, immunoglobulin genes, somatic hypermutation, Epstein-Barr virus, Medical and Health Sciences, Immunology
Abstract

Recent work identified Hodgkin and Reed-Sternberg (H/RS) cells in classical Hodgkin's disease (cHD) as clonal progeny of mature B cells. Therefore, it is generally assumed that cHD homogenously represents a B cell lymphoma. In a subset of cHD, however, H/RS cells expressing T cell-associated proteins may be candidates for alternative lineage derivation. Single H/RS cells with cytotoxic T cell phenotype were micromanipulated from three cases of cHD and analyzed by single cell polymerase chain reaction for immunoglobulin heavy (IgH) and light chain (IgL) gene rearrangements, T cell receptor (TCR)-beta gene rearrangements, and germline configuration of the IgH and TCR-beta loci. H/RS cells from two cases of cHD harbored clonal, somatically mutated Ig gene rearrangements, whereas TCR-beta loci were in germline configuration. In contrast, H/RS cells from an additional case harbored clonal TCR-beta variable/diversity/joining (VDJ) and DJ gene rearrangements, whereas the IgH locus was in germline configuration on both alleles. Thus, in two cases of cHD with H/RS cells expressing cytotoxic T cell molecules, the tumor cells are derived from mature B cells that aberrantly express T cell markers. In a third case, however, H/RS cells were derived from a T cell, demonstrating that cHD can also occur as a T cell lymphoma.

Published
2000

25. Identification of two unannotated miRNAs in classic Hodgkin lymphoma cell lines

Author

Ustaszewski Adam, Paczkowska Julia, Janiszewska Joanna, Bernhart Stephan H., Bein Julia, Russiñol Núria, Hansmann Martin-Leo, Chapaprieta Vicente, Martín-Subero José I., Siebert Reiner, Hartmann Sylvia, and Giefing Maciej

Subjects
Classic Hodgkin lymphoma (cHL), novel miRNA, loss of epigenetic control
Abstract

MicroRNAs (miRNAs) are small non coding RNAs responsible for posttranscriptional regulation of gene expression. Even though almost 2000 precursors have been described so far, additional miRNAs are still being discovered in normal as well as malignant cells. Alike protein coding genes, miRNAs may acquire oncogenic properties in consequence of altered expression or presence of gain or loss of function mutations. In this study we mined datasets from miRNA expression profiling (miRNA-seq) of 7 classic Hodgkin Lymphoma (cHL) cell lines, 10 non-Hodgkin lymphoma (NHL) cell lines and 56 samples of germinal center derived B-cell lymphomas. Our aim was to discover potential novel cHL oncomiRs not reported in miRBase (release 22.1) and expressed in cHL cell lines but no other B-cell lymphomas. We identified six such miRNA candidates in cHL cell lines and verified the expression of two of them encoded at chr2:212678788-212678849 and chr5:168090507-168090561 (GRCh38). Interestingly, we showed that one of the validated miRNAs (located in an intron of the TENM2 gene) is expressed together with its host gene. TENM2 is characterized by hypomethylation and open chromatin around its TSS in cHL cell lines in contrast to NHL cell lines and germinal centre B-cells respectively. It indicates an epigenetic mechanism responsible for aberrant expression of both, the TENM2 gene and the novel miRNA in cHL cell lines.

Published
2023

26. Molecular characteristics of diffuse large B-cell lymphoma in the Positron Emission Tomography-Guided Therapy of Aggressive Non-Hodgkin lymphomas (PETAL) trial: correlation with interim PET and outcome

Author

Richter, Julia, Hüttmann, Andreas, Rekowski, Jan, Schmitz, Christine, Gärtner, Selina, Rosenwald, Andreas, Hansmann, Martin-Leo, Hartmann, Sylvia, Möller, Peter, Wacker, Hans-Heinrich, Feller, Alfred, Thorns, Christoph, Müller, Stefan, Dührsen, Ulrich, and Klapper, Wolfram

Published
2019
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27. A modular transcriptome map of mature B cell lymphomas

Author

Loeffler-Wirth, Henry, Kreuz, Markus, Hopp, Lydia, Arakelyan, Arsen, Haake, Andrea, Cogliatti, Sergio B., Feller, Alfred C., Hansmann, Martin-Leo, Lenze, Dido, Möller, Peter, Müller-Hermelink, Hans Konrad, Fortenbacher, Erik, Willscher, Edith, Ott, German, Rosenwald, Andreas, Pott, Christiane, Schwaenen, Carsten, Trautmann, Heiko, Wessendorf, Swen, Stein, Harald, Szczepanowski, Monika, Trümper, Lorenz, Hummel, Michael, Klapper, Wolfram, Siebert, Reiner, Loeffler, Markus, Binder, Hans, and for the German Cancer Aid consortium Molecular Mechanisms for Malignant Lymphoma

Published
2019
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28. Genomic and transcriptomic changes complement each other in the pathogenesis of sporadic Burkitt lymphoma

Author

López, Cristina, Kleinheinz, Kortine, Aukema, Sietse M., Rohde, Marius, Bernhart, Stephan H., Hübschmann, Daniel, Wagener, Rabea, Toprak, Umut H., Raimondi, Francesco, Kreuz, Markus, Waszak, Sebastian M., Huang, Zhiqin, Sieverling, Lina, Paramasivam, Nagarajan, Seufert, Julian, Sungalee, Stephanie, Russell, Robert B., Bausinger, Julia, Kretzmer, Helene, Ammerpohl, Ole, Bergmann, Anke K., Binder, Hans, Borkhardt, Arndt, Brors, Benedikt, Claviez, Alexander, Doose, Gero, Feuerbach, Lars, Haake, Andrea, Hansmann, Martin-Leo, Hoell, Jessica, Hummel, Michael, Korbel, Jan O., Lawerenz, Chris, Lenze, Dido, Radlwimmer, Bernhard, Richter, Julia, Rosenstiel, Philip, Rosenwald, Andreas, Schilhabel, Markus B., Stein, Harald, Stilgenbauer, Stephan, Stadler, Peter F., Szczepanowski, Monika, Weniger, Marc A., Zapatka, Marc, Eils, Roland, Lichter, Peter, Loeffler, Markus, Möller, Peter, Trümper, Lorenz, Klapper, Wolfram, ICGC MMML-Seq Consortium, Hoffmann, Steve, Küppers, Ralf, Burkhardt, Birgit, Schlesner, Matthias, and Siebert, Reiner

Published
2019
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29. Clonal composition and differentiation stage of human CD30+ B cells in reactive lymph nodes.

Author

Küppers, Ralf, Budeus, Bettina, Hartmann, Sylvia, and Hansmann, Martin-Leo

Subjects
B cells, B cell differentiation, LYMPH nodes, LYMPHADENITIS, HODGKIN'S disease
Abstract

Introduction: Normal CD30+ B cells represent a distinct B-cell differentiation stage with features of strong activation. We lack an in depth understanding of these cells, because they are not present in peripheral blood and are typically very rare in reactive lymphoid organs. CD30+ B cells have been discussed as a potential precursor population for the malignant CD30+ Hodgkin and Reed-Sternberg cells in classical Hodgkin lymphoma. As CD30+ B cells can be more numerous in some cases of reactive lymphadenitis, we aimed to characterize these CD30+ B cells in terms of their differentiation stage and clonal composition, also as a means to clarify whether such CD30+ B-cell populations may represent potential precursor lesions of Hodgkin lymphoma. Methods: We microdissected single CD30+ B cells from tissue sections of eight reactive lymph nodes with substantial numbers of such cells and sequenced their rearranged immunoglobulin (Ig) heavy chain V region (IGHV) genes. Results: The CD30+ B cells were polyclonal B cells in all instances, and they not only encompass post-germinal center (GC) B cells with mutated IGHV genes, but also include a substantial fraction of pre-germinal center B cells with unmutated IGHV genes. In five of the lymph nodes, mostly small clonal expansions were detected among the CD30+ B cells. Most of the expanded clones carried somatically mutated IGHV genes and about half of the mutated clones showed intraclonal diversity. Discussion: We conclude that in human reactive lymph nodes with relatively many CD30+ B cells, these cells are a heterogenous population of polyclonal B cells encompassing activated pre-GC B cells as well as GC and post-GC B cells, with some clonal expansions. Because of their polyclonality and frequent pre-GC differentiation stage, there is no indication that such cell-rich CD30+ B-cell populations represent precursor lesions of Hodgkin lymphoma. [ABSTRACT FROM AUTHOR]

Published
2023
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30. P043: Molecular pathogenesis of Hodgkin lymphoma

Author

Beeck, Lilian, primary, Schneider, Markus, additional, Farsijani, Navid, additional, Budeus, Bettina, additional, Bein, Julia, additional, Schaefer, Hendrik, additional, Hartmann, Sylvia, additional, Hansmann, Martin-Leo, additional, and Küppers, Ralf, additional

Published
2022
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31. SAMHD1 is a biomarker for cytarabine response and a therapeutic target in acute myeloid leukemia

Author

Schneider, Constanze, Oellerich, Thomas, Baldauf, Hanna-Mari, Schwarz, Sarah-Marie, Thomas, Dominique, Flick, Robert, Bohnenberger, Hanibal, Kaderali, Lars, Stegmann, Lena, Cremer, Anjali, Martin, Margarethe, Lohmeyer, Julian, Michaelis, Martin, Hornung, Veit, Schliemann, Christoph, Berdel, Wolfgang E, Hartmann, Wolfgang, Wardelmann, Eva, Comoglio, Federico, Hansmann, Martin-Leo, Yakunin, Alexander F, Geisslinger, Gerd, Ströbel, Philipp, Ferreirós, Nerea, Serve, Hubert, Keppler, Oliver T, and Cinatl, Jindrich, Jr

Subjects
Cellular proteins -- Health aspects, Cytarabine -- Patient outcomes, Drug metabolism -- Genetic aspects, Acute myelocytic leukemia -- Genetic aspects -- Development and progression -- Care and treatment, Biological sciences, Health
Abstract

Author(s): Constanze Schneider [1]; Thomas Oellerich [2, 3, 4]; Hanna-Mari Baldauf [1, 5]; Sarah-Marie Schwarz [1]; Dominique Thomas [6]; Robert Flick [7]; Hanibal Bohnenberger [8]; Lars Kaderali [9]; Lena Stegmann [...]

Published
2017
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36. The prognostic impact of variant histology in nodular lymphocyte-predominant Hodgkin lymphoma: a report from the German Hodgkin Study Group (GHSG)

Author

Hartmann, Sylvia, Eichenauer, Dennis A., Plütschow, Annette, Mottok, Anja, Bob, Roshanak, Koch, Karoline, Bernd, Heinz-Wolfram, Cogliatti, Sergio, Hummel, Michael, Feller, Alfred C., Ott, German, Möller, Peter, Rosenwald, Andreas, Stein, Harald, Hansmann, Martin-Leo, Engert, Andreas, and Klapper, Wolfram

Published
2013
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37. The genomic and transcriptional landscape of primary central nervous system lymphoma

Author

Radke, Josefine, Ishaque, Naveed, Hostench, Xavier Pastor, Richter, Julia, Rosenstiel, Philip, Rosenwald, Andreas, Schilhabel, Markus, Schreiber, Stefanie, Vater, Inga, Wagener, Rabea, Siebert, Reiner, Bernhart, Stephan H, Binder, Hans, Borgoni, Simone, Doose, Gero, Eils, Roland, Hoffmann, Steve, Hopp, Lydia, Kleinheinz, Kortine, Kretzmer, Helene, Kreuz, Markus, Korbel, Jan, Langenberger, David, Loeffler, Markus, Juraeva, Dilafruz, Rosolowski, Maciej, Stadler, Peter F, Sungalee, Stephanie, Pritsch, Fabienne, Paramasivam, Nagarajan, Balasubramanian, Gnana Prakash, Schlesner, Matthias, Sahay, Shashwat, Weniger, Marc, Pehl, Debora, Koll, Randi, Radbruch, Helena, Osterloh, Anja, Korfel, Agnieszka, Misch, Martin, Onken, Julia, Faust, Katharina, Vajkoczy, Peter, Moskopp, Dag, Wang, Yawen, Jödicke, Andreas, Gu, Zuguang, Trümper, Lorenz, Anagnostopoulos, Ioannis, Lenze, Dido, Küppers, Ralf, Hummel, Michael, Schmitt, Clemens A, Wiestler, Otmar D, Wolf, Stephan, Unterberg, Andreas, Schumann, Elisa, Herold-Mende, Christel, Brors, Benedikt, Consortium, ICGC MMML-Seq, Wiemann, Stefan, Heppner, Frank, Wagner, Susanne, Haake, Andrea, Sieverling, Lina, Richter, Gesine, Lawerenz, Chris, Eils, Jürgen, Kerssemakers, Jules, Jaeger-Schmidt, Christina, Scholz, Ingrid, Bergmann, Anke K, Borst, Christoph, Braulke, Friederike, Uhrig, Sebastian, Burkhardt, Birgit, Claviez, Alexander, Dreyling, Martin, Eberth, Sonja, Einsele, Hermann, Frickhofen, Norbert, Haas, Siegfried, Hansmann, Martin-Leo, Karsch, Dennis, Klepl, Nicole, Hübschmann, Daniel, Kneba, Michael, Lisfeld, Jasmin, Mantovani-Löffler, Luisa, Rohde, Marius, Ott, German, Stadler, Christina, Staib, Peter, Stilgenbauer, Stephan, Zenz, Thorsten, Toprak, Umut H, Kube, Dieter, Klapper, Wolfram, Kostezka, Ulrike, Möller, Peter, Szczepanowski, Monika, Ammerpohl, Ole, Aukema, Sietse M, López, Cristina, Binder, Vera, Borkhardt, Arndt, Hoell, Jessica I, Leich, Ellen, Lichter, Peter, Nagel, Inga, Pischimariov, Jordan, Radlwimmer, Bernhard, Weniger, Marc (Beitragende*r), and Küppers, Ralf (Beitragende*r)

Subjects
Central Nervous System, Epstein-Barr Virus Infections, Herpesvirus 4, Human, Cancer Research, Multidisciplinary, genetics [Central Nervous System Neoplasms], Medizin, General Physics and Astronomy, pathology [Central Nervous System Neoplasms], Genomics, General Chemistry, metabolism [Lymphoma, Large B-Cell, Diffuse], General Biochemistry, Genetics and Molecular Biology, Central Nervous System Neoplasms, hemic and lymphatic diseases, metabolism [Central Nervous System], Humans, ddc:610, Lymphoma, Large B-Cell, Diffuse, ddc:500
Abstract

Primary lymphomas of the central nervous system (PCNSL) are mainly diffuse large B-cell lymphomas (DLBCLs) confined to the central nervous system (CNS). Molecular drivers of PCNSL have not been fully elucidated. Here, we profile and compare the whole-genome and transcriptome landscape of 51 CNS lymphomas (CNSL) to 39 follicular lymphoma and 36 DLBCL cases outside the CNS. We find recurrent mutations in JAK-STAT, NFkB, and B-cell receptor signaling pathways, including hallmark mutations in MYD88 L265P (67%) and CD79B (63%), and CDKN2A deletions (83%). PCNSLs exhibit significantly more focal deletions of HLA-D (6p21) locus as a potential mechanism of immune evasion. Mutational signatures correlating with DNA replication and mitosis are significantly enriched in PCNSL. TERT gene expression is significantly higher in PCNSL compared to activated B-cell (ABC)-DLBCL. Transcriptome analysis clearly distinguishes PCNSL and systemic DLBCL into distinct molecular subtypes. Epstein-Barr virus (EBV)+ CNSL cases lack recurrent mutational hotspots apart from IG and HLA-DRB loci. We show that PCNSL can be clearly distinguished from DLBCL, having distinct expression profiles, IG expression and translocation patterns, as well as specific combinations of genetic alterations.

Published
2022

38. Histopathological growth patterns in patients with advanced nodular lymphocyte-predominant Hodgkin lymphoma treated within the randomized HD18 study: a report from the German Hodgkin Study Group

Author

Eichenauer, Dennis A., Buhnen, Ina, Kreissl, Stefanie, Goergen, Helen, Fuchs, Michael, von Tresckow, Bastian, Rosenwald, Andreas, Klapper, Wolfram, Hansmann, Martin-Leo, Moller, Peter, Bernd, Heinz-Wolfram, Feller, Alfred C., Engert, Andreas, Borchmann, Peter, Hartmann, Sylvia, Eichenauer, Dennis A., Buhnen, Ina, Kreissl, Stefanie, Goergen, Helen, Fuchs, Michael, von Tresckow, Bastian, Rosenwald, Andreas, Klapper, Wolfram, Hansmann, Martin-Leo, Moller, Peter, Bernd, Heinz-Wolfram, Feller, Alfred C., Engert, Andreas, Borchmann, Peter, and Hartmann, Sylvia

Abstract

We retrospectively investigated histopathological growth patterns in individuals with advanced nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) treated within the randomized HD18 study. In all, 35/60 patients (58%) presented with atypical growth patterns. Patients with atypical growth patterns more often had stage IV disease (P = 0 center dot 0354) and splenic involvement (P = 0 center dot 0048) than patients with typical growth patterns; a positive positron emission tomography after two cycles of chemotherapy (PET-2) tended to be more common (P = 0 center dot 1078). Five-year progression-free survival [hazard ratio (HR) = 0 center dot 86; 95% confidence interval (CI) = 0 center dot 49-1 center dot 47] and overall survival (HR = 0 center dot 85; 95% CI = 0 center dot 49-1 center dot 51) did not differ between the groups after study treatment with PET-2-guided escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone). Thus, advanced NLPHL is often associated with atypical growth patterns but their prognostic impact is compensated by PET-2-guided escalated BEACOPP.

Published
2022

39. Loss of function mutations of BCOR in classical Hodgkin lymphoma

Author

Giefing, Maciej, Gearhart, Micah D., Schneider, Markus, Overbeck, Birte, Klapper, Wolfram, Hartmann, Sylvia, Ustaszewski, Adam, Weniger, Marc A., Wiehle, Laura, Hansmann, Martin-Leo, Melnick, Ari, Beguelin, Wendy, Sundström, Christer, Küppers, Ralf, Bardwell, Vivian J., Siebert, Reiner, Giefing, Maciej, Gearhart, Micah D., Schneider, Markus, Overbeck, Birte, Klapper, Wolfram, Hartmann, Sylvia, Ustaszewski, Adam, Weniger, Marc A., Wiehle, Laura, Hansmann, Martin-Leo, Melnick, Ari, Beguelin, Wendy, Sundström, Christer, Küppers, Ralf, Bardwell, Vivian J., and Siebert, Reiner

Abstract

BCOR is a component of a variant Polycomb repressive complex 1 (PRC1.1). PRC1 and PRC2 complexes together constitute a major gene regulatory system critical for appropriate cellular differentiation. The gene is upregulated in germinal center (GC) B cells and mutated in a number of hematologic malignancies. We report BCOR inactivating alterations in 4/7 classic Hodgkin lymphoma (cHL) cell lines, subclonal somatic mutations in Hodgkin and Reed-Sternberg (HRS) cells of 4/10 cHL cases, and deletions in HRS cells of 7/17 primary cHL cases. In mice, conditional loss of Bcor driven by AID-Cre in GC B cells resulted in gene expression changes of 46 genes (>2-fold) including upregulated Lef1 that encodes a transcription factor responsible for establishing T-cell identity and Il9r (interleukin-9 receptor), an important member of the cytokine network in cHL. Our findings suggest a role for BCOR loss in cHL pathogenesis and GC-B cell homeostasis.

Published
2022
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40. T-cell-derived Hodgkin lymphoma has motility characteristics intermediate between Hodgkin and anaplastic large cell lymphoma

Author

Bein, Julia, Flinner, Nadine, Häupl, Björn, Mathur, Aastha, Schneider, Olga, Abu-Ayyad, Marwa, Hansmann, Martin-Leo, Piel, Matthieu, Oellerich, Thomas, Hartmann, Sylvia, Bein, Julia, Flinner, Nadine, Häupl, Björn, Mathur, Aastha, Schneider, Olga, Abu-Ayyad, Marwa, Hansmann, Martin-Leo, Piel, Matthieu, Oellerich, Thomas, and Hartmann, Sylvia

Abstract

Classic Hodgkin lymphoma (cHL) is usually characterized by a low tumour cell content, derived from crippled germinal centre B cells. Rare cases have been described in which the tumour cells show clonal T-cell receptor rearrangements. From a clinicopathological perspective, it is unclear if these cases should be classified as cHL or anaplastic large T-cell lymphoma (ALCL). Since we recently observed differences in the motility of ALCL and cHL tumour cells, here, we aimed to obtain a better understanding of T-cell-derived cHL by investigating their global proteomic profiles and their motility. In a proteomics analysis, when only motility-associated proteins were regarded, T-cell-derived cHL cell lines showed the highest similarity to ALK− ALCL cell lines. In contrast, T-cell-derived cHL cell lines presented a very low overall motility, similar to that observed in conventional cHL. Whereas all ALCL cell lines, as well as T-cell-derived cHL, predominantly presented an amoeboid migration pattern with uropod at the rear, conventional cHL never presented with uropods. The migration of ALCL cell lines was strongly impaired upon application of different inhibitors. This effect was less pronounced in cHL cell lines and almost invisible in T-cell-derived cHL. In summary, our cell line-derived data suggest that based on proteomics and migration behaviour, T-cell-derived cHL is a neoplasm that shares features with both cHL and ALCL and is not an ALCL with low tumour cell content. Complementary clinical studies on this lymphoma are warranted.

Published
2022

41. Tumour cell characteristics and microenvironment composition correspond to clinical presentation in newly diagnosed nodular lymphocyte-predominant Hodgkin lymphoma

Author

Hartmann, Sylvia, Soltani, Ahmad Sajad, Bankov, Katrin, Bein, Julia, Hansmann, Martin-Leo, Rosenwald, Andreas, Bernd, Heinz-Wolfram, Feller, Alfred, Ott, German, Moeller, Peter, Stein, Harald, Klapper, Wolfram, Borchmann, Peter, Engert, Andreas, Eichenauer, Dennis A., Hartmann, Sylvia, Soltani, Ahmad Sajad, Bankov, Katrin, Bein, Julia, Hansmann, Martin-Leo, Rosenwald, Andreas, Bernd, Heinz-Wolfram, Feller, Alfred, Ott, German, Moeller, Peter, Stein, Harald, Klapper, Wolfram, Borchmann, Peter, Engert, Andreas, and Eichenauer, Dennis A.

Abstract

Different studies have characterized the microenvironment and its prognostic impact in classic Hodgkin lymphoma whereas such analyses are pending for nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). We thus investigated characteristics of tumour cells and microenvironment in NLPHL and evaluated possible correlations with the clinical presentation. Lymph node samples from 152 NLPHL patients who had first-line treatment within the randomized German Hodgkin Study Group HD16-HD18 trials were available and analysed with regard to IgD status and nuclear size of the tumour cells as well as presence of PD1-positive follicular T helper cells and CD163-positive macrophages in the microenvironment. While large tumour cell nuclei and high numbers of PD1-positive follicular T helper cells in the microenvironment were more common in patients presenting with early/intermediate stages than in patients with advanced-stage disease (p < 0.0001, unpaired t-test; p = 0.0022, Mann-Whitney test), no differences between risk groups were observed in terms of the IgD status of the tumour cells and the content of CD163-positive macrophages in the microenvironment. PD1-positive follicular T helper cells were present in both cases with typical and variant growth patterns and rosetting around the tumour cells was observed in 96% of patients, indicating an important role of PD1-positive follicular T helper cells in NLPHL.

Published
2022

42. B‐cell receptors of EBV‐negative Burkitt lymphoma bind modified isoforms of autoantigens

Author

Bock, Theresa, primary, Bewarder, Moritz, additional, Cetin, Onur, additional, Fadle, Natalie, additional, Regitz, Evi, additional, Schwarz, Eva C., additional, Held, Jana, additional, Roth, Sophie, additional, Lohse, Stefan, additional, Pfuhl, Thorsten, additional, Wagener, Rabea, additional, Smola, Sigrun, additional, Becker, Sören L., additional, Bohle, Rainer Maria, additional, Trümper, Lorenz, additional, Siebert, Reiner, additional, Hansmann, Martin‐Leo, additional, Pfreundschuh, Michael, additional, Drexler, Hans G., additional, Hoth, Markus, additional, Kubuschok, Boris, additional, Roemer, Klaus, additional, Preuss, Klaus‐Dieter, additional, Hartmann, Sylvia, additional, and Thurner, Lorenz, additional

Published
2022
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45. MYC status in concert with BCL2 and BCL6 expression predicts outcome in diffuse large B-cell lymphoma

Author

Horn, Heike, Ziepert, Marita, Becher, Claudia, Barth, Thomas F.E., Bernd, Heinz-Wolfram, Feller, Alfred C., Klapper, Wolfram, Hummel, Michael, Stein, Harald, Hansmann, Martin-Leo, Schmelter, Christopher, Möller, Peter, Cogliatti, Sergio, Pfreundschuh, Michael, Schmitz, Norbert, Trümper, Lorenz, Siebert, Reiner, Loeffler, Markus, Rosenwald, Andreas, and Ott, German

Published
2013
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47. Divergent Effects of EZH1 and EZH2 Protein Expression on the Prognosis of Patients with T-Cell Lymphomas

Author

Schümann, Franziska Lea, primary, Groß, Elisabeth, additional, Bauer, Marcus, additional, Rohde, Christian, additional, Sandmann, Sarah, additional, Terziev, Denis, additional, Müller, Lutz P., additional, Posern, Guido, additional, Wienke, Andreas, additional, Fend, Falko, additional, Hansmann, Martin-Leo, additional, Klapper, Wolfram, additional, Rosenwald, Andreas, additional, Stein, Harald, additional, Dugas, Martin, additional, Müller-Tidow, Carsten, additional, Wickenhauser, Claudia, additional, Binder, Mascha, additional, and Weber, Thomas, additional

Published
2021
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48. Landscape of 4D Cell Interaction in Hodgkin and Non-Hodgkin Lymphomas

Author

Hartmann, Sylvia, primary, Scharf, Sonja, additional, Steiner, Yvonne, additional, Loth, Andreas G., additional, Donnadieu, Emmanuel, additional, Flinner, Nadine, additional, Poeschel, Viola, additional, Angel, Stephanie, additional, Bewarder, Moritz, additional, Bein, Julia, additional, Brunnberg, Uta, additional, Bozzato, Alessandro, additional, Schick, Bernhard, additional, Stilgenbauer, Stephan, additional, Bohle, Rainer M., additional, Thurner, Lorenz, additional, and Hansmann, Martin-Leo, additional

Published
2021
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49. Immunoblastic morphology but not the immunohistochemical GCB/nonGCB classifier predicts outcome in diffuse large B-cell lymphoma in the RICOVER-60 trial of the DSHNHL

Author

Ott, German, Ziepert, Marita, Klapper, Wolfram, Horn, Heike, Szczepanowski, Monika, Bernd, Heinz-Wolfram, Thorns, Christoph, Feller, Alfred C., Lenze, Dido, Hummel, Michael, Stein, Harald, Müller-Hermelink, Hans-Konrad, Frank, Matthias, Hansmann, Martin-Leo, Barth, Thomas F.E., Möller, Peter, Cogliatti, Sergio, Pfreundschuh, Michael, Schmitz, Norbert, Trümper, Lorenz, Loeffler, Markus, and Rosenwald, Andreas

Published
2010
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