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4. Concept and feasibility of the Augsburg Longitudinal Plasma Study (ALPS) – a prospective trial for comprehensive liquid biopsy-based longitudinal monitoring of solid cancer patients

Author

Sommer Sebastian, Schmutz Maximilian, Hildebrand Kathrin, Schiwitza Annett, Benedikt Selinah, Eberle Maria, Mögele Tatiana, Sultan Aziz, Reichl Lena, Campillo Maria, Uhrmacher Luise, Nikolic Ana Antic, Bundschuh Ralph, Lapa Constantin, Kuhlen Michaela, Dintner Sebastian, Langer Angela, Märkl Bruno, Wendler Thomas, Tehlan Kartikay, Kröncke Thomas, Wahle Maria, Mann Matthias, Casadei Nicolas, Pogoda Michaela, Hummler Simone, Sax Irmengard, Schlesner Matthias, Kubuschok Boris, Trepel Martin, and Claus Rainer

Subjects
liquid biopsy, ctdna, longitudinal profiling, clonal evolution, spatial heterogeneity, translational research, Medical technology, R855-855.5
Abstract

Liquid biopsy (LBx) provides diagnostic, prognostic and predictive insights for malignant diseases and offers promising applications regarding tumor burden, tumor heterogeneity and clonal evolution.

Published
2024
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5. Benchmarking whole exome sequencing in the German network for personalized medicine

Author

Menzel, Michael, Martis-Thiele, Mihaela, Goldschmid, Hannah, Ott, Alexander, Romanovsky, Eva, Siemanowski-Hrach, Janna, Seillier, Lancelot, Brüchle, Nadina Ortiz, Maurer, Angela, Lehmann, Kjong-Van, Begemann, Matthias, Elbracht, Miriam, Meyer, Robert, Dintner, Sebastian, Claus, Rainer, Meier-Kolthoff, Jan P., Blanc, Eric, Möbs, Markus, Joosten, Maria, Benary, Manuela, Basitta, Patrick, Hölscher, Florian, Tischler, Verena, Groß, Thomas, Kutz, Oliver, Prause, Rebecca, William, Doreen, Horny, Kai, Goering, Wolfgang, Sivalingam, Sugirthan, Borkhardt, Arndt, Blank, Cornelia, Junk, Stefanie V., Yasin, Layal, Moskalev, Evgeny A., Carta, Maria Giulia, Ferrazzi, Fulvia, Tögel, Lars, Wolter, Steffen, Adam, Eugen, Matysiak, Uta, Rosenthal, Tessa, Dönitz, Jürgen, Lehmann, Ulrich, Schmidt, Gunnar, Bartels, Stephan, Hofmann, Winfried, Hirsch, Steffen, Dikow, Nicola, Göbel, Kirsten, Banan, Rouzbeh, Hamelmann, Stefan, Fink, Annette, Ball, Markus, Neumann, Olaf, Rehker, Jan, Kloth, Michael, Murtagh, Justin, Hartmann, Nils, Jurmeister, Phillip, Mock, Andreas, Kumbrink, Jörg, Jung, Andreas, Mayr, Eva-Maria, Jacob, Anne, Trautmann, Marcel, Kirmse, Santina, Falkenberg, Kim, Ruckert, Christian, Hirsch, Daniela, Immel, Alexander, Dietmaier, Wolfgang, Haack, Tobias, Marienfeld, Ralf, Fürstberger, Axel, Niewöhner, Jakob, Gerstenmaier, Uwe, Eberhardt, Timo, Greif, Philipp A., Appenzeller, Silke, Maurus, Katja, Doll, Julia, Jelting, Yvonne, Jonigk, Danny, Märkl, Bruno, Beule, Dieter, Horst, David, Wulf, Anna-Lena, Aust, Daniela, Werner, Martin, Reuter-Jessen, Kirsten, Ströbel, Philipp, Auber, Bernd, Sahm, Felix, Merkelbach-Bruse, Sabine, Siebolts, Udo, Roth, Wilfried, Lassmann, Silke, Klauschen, Frederick, Gaisa, Nadine T., Weichert, Wilko, Evert, Matthias, Armeanu-Ebinger, Sorin, Ossowski, Stephan, Schroeder, Christopher, Schaaf, Christian P., Malek, Nisar, Schirmacher, Peter, Kazdal, Daniel, Pfarr, Nicole, Budczies, Jan, and Stenzinger, Albrecht

Published
2024
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8. The WERA cancer center matrix: Strategic management of patient access to precision oncology in a large and mostly rural area of Germany

Author

Krebs, Markus, Haller, Florian, Spörl, Silvia, Gerhard-Hartmann, Elena, Utpatel, Kirsten, Maurus, Katja, Kunzmann, Volker, Chatterjee, Manik, Venkataramani, Vivek, Maatouk, Imad, Bittrich, Max, Einwag, Tatjana, Meidenbauer, Norbert, Tögel, Lars, Hirsch, Daniela, Dietmaier, Wolfgang, Keil, Felix, Scheiter, Alexander, Immel, Alexander, Heudobler, Daniel, Einhell, Sabine, Kaiser, Ulrich, Sedlmeier, Anja M., Maurer, Julia, Schenkirsch, Gerhard, Jordan, Frank, Schmutz, Maximilian, Dintner, Sebastian, Rosenwald, Andreas, Hartmann, Arndt, Evert, Matthias, Märkl, Bruno, Bargou, Ralf, Mackensen, Andreas, Beckmann, Matthias W., Pukrop, Tobias, Herr, Wolfgang, Einsele, Hermann, Trepel, Martin, Goebeler, Maria-Elisabeth, Claus, Rainer, Kerscher, Alexander, and Lüke, Florian

Published
2024
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10. Other malignancies in the history of CLL: an international multicenter study conducted by ERIC, the European Research Initiative on CLL, in HARMONY

Author

Chatzikonstantinou, Thomas, Scarfò, Lydia, Karakatsoulis, Georgios, Minga, Eva, Chamou, Dimitra, Iacoboni, Gloria, Kotaskova, Jana, Demosthenous, Christos, Smolej, Lukas, Mulligan, Stephen, Alcoceba, Miguel, Al-Shemari, Salem, Aurran-Schleinitz, Thérèse, Bacchiarri, Francesca, Bellido, Mar, Bijou, Fontanet, Calleja, Anne, Medina, Angeles, Khan, Mehreen Ali, Cassin, Ramona, Chatzileontiadou, Sofia, Collado, Rosa, Christian, Amy, Davis, Zadie, Dimou, Maria, Donaldson, David, Santos, Gimena Dos, Dreta, Barbara, Efstathopoulou, Maria, El-Ashwah, Shaimaa, Enrico, Alicia, Fresa, Alberto, Galimberti, Sara, Galitzia, Andrea, García-Serra, Rocío, Gimeno, Eva, González-Gascón-y-Marín, Isabel, Gozzetti, Alessandro, Guarente, Valerio, Guieze, Romain, Gogia, Ajay, Gupta, Ritu, Harrop, Sean, Hatzimichael, Eleftheria, Herishanu, Yair, Hernández-Rivas, José-Ángel, Inchiappa, Luca, Jaksic, Ozren, Janssen, Susanne, Kalicińska, Elżbieta, Laribi, Kamel, Karakus, Volkan, Kater, Arnon P., Kho, Bonnie, Kislova, Maria, Konstantinou, Eliana, Koren-Michowitz, Maya, Kotsianidis, Ioannis, Kreitman, Robert J., Labrador, Jorge, Lad, Deepesh, Levin, Mark-David, Levy, Ilana, Longval, Thomas, Lopez-Garcia, Alberto, Marquet, Juan, Martin-Rodríguez, Lucia, Maynadié, Marc, Maslejova, Stanislava, Mayor-Bastida, Carlota, Mihaljevic, Biljana, Milosevic, Ivana, Miras, Fatima, Moia, Riccardo, Morawska, Marta, Murru, Roberta, Nath, Uttam Kumar, Navarro-Bailón, Almudena, Oliveira, Ana C., Olivieri, Jacopo, Oscier, David, Panovska-Stavridis, Irina, Papaioannou, Maria, Papajík, Tomas, Kubova, Zuzana, Phumphukhieo, Punyarat, Pierie, Cheyenne, Puiggros, Anna, Rani, Lata, Reda, Gianluigi, Rigolin, Gian Matteo, Ruchlemer, Rosa, Daniel de Deus Santos, Marcos, Schipani, Mattia, Schiwitza, Annett, Shen, Yandong, Simkovic, Martin, Smirnova, Svetlana, Abdelrahman Soliman, Dina Sameh, Spacek, Martin, Tadmor, Tamar, Tomic, Kristina, Tse, Eric, Vassilakopoulos, Theodoros, Visentin, Andrea, Vitale, Candida, von Tresckow, Julia, Vrachiolias, George, Vukovic, Vojin, Walewska, Renata, Wasik-Szczepanek, Ewa, Xu, Zhenshu, Yagci, Munci, Yañez, Lucrecia, Yassin, Mohamed, Zuchnicka, Jana, Angelopoulou, Maria, Antic, Darko, Biderman, Bella, Catherwood, Mark, Claus, Rainer, Coscia, Marta, Cuneo, Antonio, Demirkan, Fatih, Espinet, Blanca, Gaidano, Gianluca, Kalashnikova, Olga B., Laurenti, Luca, Nikitin, Eugene, Pangalis, Gerassimos A., Panagiotidis, Panagiotis, Popov, Viola Maria, Pospisilova, Sarka, Sportoletti, Paolo, Stavroyianni, Niki, Tam, Constantine, Trentin, Livio, Chatzidimitriou, Anastasia, Bosch, Francesc, Doubek, Michael, Ghia, Paolo, and Stamatopoulos, Kostas

Published
2023
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11. Netboost: Boosting-supported network analysis improves high-dimensional omics prediction in acute myeloid leukemia and Huntington's disease

Author

Schlosser, Pascal, Knaus, Jochen, Schmutz, Maximilian, Döhner, Konstanze, Plass, Christoph, Bullinger, Lars, Claus, Rainer, Binder, Harald, Lübbert, Michael, and Schumacher, Martin

Subjects
Quantitative Biology - Genomics, Statistics - Applications, Statistics - Methodology
Abstract

Background: State-of-the art selection methods fail to identify weak but cumulative effects of features found in many high-dimensional omics datasets. Nevertheless, these features play an important role in certain diseases. Results: We present Netboost, a three-step dimension reduction technique. First, a boosting-based filter is combined with the topological overlap measure to identify the essential edges of the network. Second, sparse hierarchical clustering is applied on the selected edges to identify modules and finally module information is aggregated by the first principal components. The primary analysis is than carried out on these summary measures instead of the original data. We demonstrate the application of the newly developed Netboost in combination with CoxBoost for survival prediction of DNA methylation and gene expression data from 180 acute myeloid leukemia (AML) patients and show, based on cross-validated prediction error curve estimates, its prediction superiority over variable selection on the full dataset as well as over an alternative clustering approach. The identified signature related to chromatin modifying enzymes was replicated in an independent dataset of AML patients in the phase II AMLSG 12-09 study. In a second application we combine Netboost with Random Forest classification and improve the disease classification error in RNA-sequencing data of Huntington's disease mice. Conclusion: Netboost improves definition of predictive variables for survival analysis and classification. It is a freely available Bioconductor R package for dimension reduction and hypothesis generation in high-dimensional omics applications.

Published
2019
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13. Refractory and relapsed paediatric ACC in the MET studies – A challenging situation necessitating novel diagnostic and therapeutic concepts

Author

Kuhlen, Michaela, Kunstreich, Marina, Lessel, Lienhard, Wudy, Stefan A., Holterhus, Paul-Martin, Vokuhl, Christian, Juettner, Eva, Roecken, Christoph, Seitz, Guido, Slavetinsky, Christoph, Fuchs, Jörg, Schewe, Denis M., Claus, Rainer, Johann, Pascal D., Frühwald, Michael C., Vorwerk, Peter, and Redlich, Antje

Published
2023
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14. High viral loads: what drives fatal cases of COVID-19 in vaccinees? – an autopsy study

Author

Hirschbühl, Klaus, Schaller, Tina, Märkl, Bruno, Claus, Rainer, Sipos, Eva, Rentschler, Lukas, Maccagno, Andrea, Grosser, Bianca, Kling, Elisabeth, Neidig, Michael, Kröncke, Thomas, Spring, Oliver, Braun, Georg, Bösmüller, Hans, Seidl, Maximilian, Esposito, Irene, Pablik, Jessica, Hilsenbeck, Julia, Boor, Peter, Beer, Martin, Dintner, Sebastian, and Wylezich, Claudia

Published
2022
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17. Double Heterozygous Pathogenic Variants in TP53 and CHEK2 in Boy with Undifferentiated Embryonal Sarcoma of the Liver.

Author

Kuhlen, Michaela, Schaller, Tina, Dintner, Sebastian, Stadler, Nicole, Hofmann, Thomas G., Schmutz, Maximilian, Claus, Rainer, Frühwald, Michael C., and Golas, Monika M.

Subjects
CHECKPOINT kinase 2, GENETIC variation, NUCLEOTIDE sequencing, GERM cells, SARCOMA
Abstract

Undifferentiated embryonal sarcoma of the liver is a rare mesenchymal malignancy that predominantly occurs in children. The relationship between this tumor entity and germline pathogenic variants (PVs) remains undefined. Here, we present the clinical case of a male patient diagnosed with undifferentiated embryonal sarcoma of the liver. Both germline and tumor samples were analyzed using next-generation sequencing. In the tumor tissue, PVs in TP53 (NM_000546.5):c.532del p.(His178Thrfs*69) and CHEK2 (NM_007194.4):c.85C>T p.(Gln29*) were identified, with both confirmed to be of germline origin. Copy number analyses indicated a loss of the wildtype TP53 allele in the tumor, consistent with a second hit, while it was the variant CHEK2 allele that was lost in the tumor. Our data indicate that the germline TP53 PV acts as a driver of tumorigenesis in the reported case and support a complex interaction between the germline TP53 and CHEK2 PVs. This case highlights the dynamic interplays of genetic alterations in tumorigenesis and emphasizes the need for continued investigation into the complex interactions between TP53 and CHEK2 PVs and into the association of undifferentiated embryonal sarcoma of the liver and Li–Fraumeni syndrome. [ABSTRACT FROM AUTHOR]

Published
2024
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18. Liver-FDG-uptake and CAR T-cell kinetics augment early PET/CT prognostic value for CD19-targeted CAR T-cell therapy in diffuse large B cell lymphoma

Author

Beck, Michael, primary, Blumenberg, Viktoria, additional, Bücklein, Veit, additional, Bundschuh, Ralph, additional, Harrer, Dennis, additional, Hirschbühl, Klaus, additional, Jung, Johannes, additional, Kunz, Wolfgang, additional, Menhart, Karin, additional, Winkelmann, Michael, additional, Yakushev, Igor, additional, Illert, Anna Lena, additional, Eckstein, Markus, additional, Völkl, Simon, additional, Claus, Rainer, additional, Hansmann, Leo, additional, Hecker, Judith, additional, Kuwert, Torsten, additional, Mackensen, Andreas, additional, Subklewe, Marion, additional, Hellwig, Dirk, additional, and Müller, Fabian, additional

Published
2024
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20. Polatuzumab vedotin as a salvage and bridging treatment in relapsed or refractory large B-cell lymphomas

Author

Liebers, Nora, Duell, Johannes, Fitzgerald, Donnacha, Kerkhoff, Andrea, Noerenberg, Daniel, Kaebisch, Eva, Acker, Fabian, Fuhrmann, Stephan, Leng, Corinna, Welslau, Manfred, Chemnitz, Jens, Middeke, Jan-Moritz, Weber, Thomas, Holtick, Udo, Trappe, Ralf, Pfannes, Roald, Liersch, Ruediger, Spoer, Christian, Fuxius, Stefan, Gebauer, Niklas, Caillé, Léandra, Geer, Thomas, Koenecke, Christian, Keller, Ulrich, Claus, Rainer, Mougiakakos, Dimitrios, Mayer, Stephanie, Huettmann, Andreas, Pott, Christiane, Trummer, Arne, Wulf, Gerald, Brunnberg, Uta, Bullinger, Lars, Hess, Georg, Mueller-Tidow, Carsten, Glass, Bertram, Lenz, Georg, Dreger, Peter, and Dietrich, Sascha

Published
2021
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22. The WERA Cancer Center Matrix: Strategic Management of Patient Access to Precision Oncology in a Large and Mostly Rural Area of Germany

Author

Krebs, Markus, primary, Haller, Florian, additional, Spoerl, Silvia, additional, Gerhard-Hartmann, Elena, additional, Utpatel, Kirsten, additional, Maurus, Katja, additional, Kunzmann, Volker, additional, Chatterjee, Manik, additional, Venkataramani, Vivek, additional, Maatouk, Imad, additional, Bittrich, Max, additional, Einwag, Tatjana, additional, Meidenbauer, Norbert, additional, Toegel, Lars, additional, Hirsch, Daniela, additional, Dietmaier, Wolfgang, additional, Keil, Felix, additional, Scheiter, Alexander, additional, Immel, Alexander, additional, Heudobler, Daniel, additional, Einhell, Sabine, additional, Kaiser, Ulrich, additional, Sedlmeier, Anja M., additional, Maurer, Julia, additional, Schenkirsch, Gerhard, additional, Jordan, Frank, additional, Schmutz, Maximilian, additional, Dintner, Sebastian, additional, Rosenwald, Andreas, additional, Hartmann, Arndt, additional, Evert, Matthias, additional, Maerkl, Bruno, additional, Bargou, Ralf, additional, Mackensen, Andreas, additional, Beckmann, Matthias W., additional, Pukrop, Tobias, additional, Herr, Wolfgang, additional, Einsele, Hermann, additional, Trepel, Martin, additional, Goebeler, Maria-Elisabeth, additional, Claus, Rainer, additional, Kerscher, Alexander, additional, and Lueke, Florian, additional

Published
2024
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24. Evolution of DNA Methylation Is Linked to Genetic Aberrations in Chronic Lymphocytic Leukemia

Author

Oakes, Christopher C, Claus, Rainer, Gu, Lei, Assenov, Yassen, Hüllein, Jennifer, Zucknick, Manuela, Bieg, Matthias, Brocks, David, Bogatyrova, Olga, Schmidt, Christopher R, Rassenti, Laura, Kipps, Thomas J, Mertens, Daniel, Lichter, Peter, Döhner, Hartmut, Stilgenbauer, Stephan, Byrd, John C, Zenz, Thorsten, and Plass, Christoph

Subjects
Rare Diseases, Genetic Testing, Genetics, Cancer, Lymphoma, Human Genome, Hematology, Good Health and Well Being, Aged, Chromosomes, Human, CpG Islands, DNA Methylation, Disease Progression, Epigenesis, Genetic, Female, Gene Expression Regulation, Leukemic, Genetic Heterogeneity, Genome, Human, Genomic Instability, Humans, Leukemia, Lymphocytic, Chronic, B-Cell, Male, Middle Aged, Oncology and Carcinogenesis
Abstract

Although clonal selection by genetic driver aberrations in cancer is well documented, the ability of epigenetic alterations to promote tumor evolution is undefined. We used 450k arrays and next-generation sequencing to evaluate intratumor heterogeneity and evolution of DNA methylation and genetic aberrations in chronic lymphocytic leukemia (CLL). CLL cases exhibit vast interpatient differences in intratumor methylation heterogeneity, with genetically clonal cases maintaining low methylation heterogeneity and up to 10% of total CpGs in a monoallelically methylated state. Increasing methylation heterogeneity correlates with advanced genetic subclonal complexity. Selection of novel DNA methylation patterns is observed only in cases that undergo genetic evolution, and independent genetic evolution is uncommon and is restricted to low-risk alterations. These results reveal that although evolution of DNA methylation occurs in high-risk, clinically progressive cases, positive selection of novel methylation patterns entails coevolution of genetic alteration(s) in CLL.

Published
2014

25. Individualized targeted treatment in a case of a rare TFG::ROS1 fusion positive inflammatory myofibroblastic tumor (IMT)

Author

Sommer, Sebastian, primary, Schmutz, Maximilian, additional, Schaller, Tina, additional, Mayr, Patrick, additional, Dintner, Sebastian, additional, Märkl, Bruno, additional, Huss, Ralf, additional, Golas, M. Monika, additional, Kuhlen, Michaela, additional, Jordan, Frank, additional, Claus, Rainer, additional, and Heinrich, Bernhard, additional

Published
2023
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26. Designing and Implementing the MySusCof App—A Mobile App to Support Food Waste Reduction

Author

Rainer Haas, Hakan Aşan, Onur Doğan, Claus Rainer Michalek, Özlem Karaca Akkan, and Zeki Atıl Bulut

Subjects
mobile app, food waste, consumer behavior, food consumption, Chemical technology, TP1-1185
Abstract

Consumers are responsible for almost 50 percent of food waste. Consumer-focused interventions are crucial to achieve many Sustainable Development Goals (SDGs), especially SDG 12.3. There are many factors that cause food waste, and these can be prevented by changing the consumption behavior of adults. Mobile apps are seen as promising tools to change consumer behavior for ensuring more sustainable food consumption. This study describes the development process and examines the perceived quality of MySusCof, an app intended to reduce the food waste of consumers. The uMARS scale was used for collecting data from consumers. Within the scope of the study, two studies were conducted to examine the development process of the application and to determine the user reactions to the mobile application. Results show that gamification elements with hedonic and social components, as well as functional aspects, are important features for user engagement and perceived impact. The qualitative results also supported the user experience in both hedonic and functional value and role of mobile apps to lead behavior change. This study serves as a guideline for future developers of mobile apps intended to lead consumers to a more sustainable food consumption.

Published
2022
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27. Decitabine in combination with donor lymphocyte infusions can induce remissions in relapsed myeloid malignancies with higher leukemic burden after allogeneic hematopoietic cell transplantation

Author

Sommer, Sebastian, Cruijsen, Marjan, Claus, Rainer, Bertz, Hartmut, Wäsch, Ralph, Marks, Reinhard, Zeiser, Robert, Bogatyreva, Lioudmila, Blijlevens, Nicole M.A., May, Annette, Duyster, Justus, Huls, Gerwin, van der Velden, Walter J.F.M., Finke, Jürgen, and Lübbert, Michael

Published
2018
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29. Embryonic stem cell factor FOXD3 (Genesis) defects in gastrointestinal stromal tumors

Author

Faucz, Fabio R, primary, Horvath, Anelia D., additional, Assié, Guillaume, additional, Almeida, Madson Q, additional, Szarek, Eva, additional, Boikos, Sosipatros, additional, Angelousi, Anna, additional, Levy, Isaac, additional, Maria, Andrea G, additional, Chitnis, Ajay, additional, Antonescu, Cristina, additional, Claus, Rainer, additional, Bertherat, Jérôme, additional, Plass, Christoph, additional, Eng, Charis, additional, and Stratakis, Constantine A, additional

Published
2023
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30. S122: MUTANT IDH1 HIJACKS DIFFERENTIATION PROGRAMS IN MYELOID PROGENITOR CELLS TO IMPAIR GRANULOCYTIC DIFFERENTIATION.

Author

Hakobyan, Mariam, primary, Langstein, Jens, additional, Kleinert, Emely, additional, Schönung, Maximilian, additional, Hartmann, Mark, additional, Rohdjess, Hannah, additional, Staeble, Sina, additional, Claus, Rainer, additional, Bullinger, Lars, additional, Oakes, Christopher, additional, Rippe, Karsten, additional, Fröhling, Stefan, additional, Pusch, Stefan, additional, Plass, Christoph, additional, Milsom, Michael, additional, and Lipka, Daniel B., additional

Published
2023
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31. S149: OTHER MALIGNANCIES IN THE HISTORY OF CLL: THE FINAL ANALYSIS OF THE INTERNATIONAL MULTICENTER STUDY CONDUCTED BY ERIC, IN HARMONY.

Author

Chatzikonstantinou, Thomas, primary, Scarfò, Lydia, additional, Karakatsoulis, Georgios, additional, Minga, Eva, additional, Chamou, Dimitra, additional, Iacoboni, Gloria, additional, Kotaskova, Jana, additional, Demosthenous, Christos, additional, Alcoceba, Miguel, additional, Al-Shemari, Salem, additional, Aurran-Schleinitz, Thérèse, additional, Bacchiarri, Francesca, additional, Bellido, Mar, additional, Bijou, Fontanet, additional, Calleja, Anne, additional, Medina, Angeles, additional, Khan, Mehreen Ali, additional, Cassin, Ramona, additional, Chatzileontiadou, Sofia, additional, Collado, Rosa, additional, Davis, Zadie, additional, Dimou, Maria, additional, Donaldson, David, additional, Santos, Gimena Dos, additional, Dreta, Barbara, additional, Efstathopoulou, Maria, additional, El-Ashwah, Shaimaa, additional, Enrico, Alicia, additional, Fresa, Alberto, additional, Galimberti, Sara, additional, Galitzia, Andrea, additional, García-Serra, Rocío, additional, Gimeno, Eva, additional, González-Gascón-Y-Marín, Isabel, additional, Gozzetti, Alessandro, additional, Guarente, Valerio, additional, Guieze, Romain, additional, Gogia, Ajay, additional, Gupta, Ritu, additional, Harrop, Sean, additional, Hatzimichael, Eleftheria, additional, Herishanu, Yair, additional, Hernández-Rivas, José-Ángel, additional, Inchiappa, Luca, additional, Jaksic, Ozren, additional, Janssen, Susanne, additional, Kalicińska, Elżbieta, additional, Kamel, Laribi, additional, Karakus, Volkan, additional, Kater, Arnon P, additional, Kho, Bonnie, additional, Kislova, Maria, additional, Konstantinou, Εliana, additional, Koren-Michowitz, Maya, additional, Kotsianidis, Ioannis, additional, Kreitman, Robert J, additional, Labrador, Jorge, additional, Lad, Deepesh, additional, Levin, Mark-David, additional, Levy, Ilana, additional, Longval, Thomas, additional, Lopez-Garcia, Alberto, additional, Marquet, Juan, additional, Maynadié, Marc, additional, Maslejova, Stanislava, additional, Mayor-Bastida, Carlota, additional, Mihaljevic, Biljana, additional, Milosevic, Ivana, additional, Miras, Fatima, additional, Moia, Riccardo, additional, Morawska, Marta, additional, Murru, Roberta, additional, Nath, Uttam Kumar, additional, Navarro-Bailón, Almudena, additional, Oliveira, Ana C., additional, Olivieri, Jacopo, additional, Oscier, David, additional, Panovska-Stavridis, Irina, additional, Papaioannou, Maria, additional, Papajík, Tomas, additional, Phumphukhieo, Punyarat, additional, Pierie, Cheyenne, additional, Puiggros, Anna, additional, Rani, Lata, additional, Reda, Gianluigi, additional, Rigolin, Gian Matteo, additional, Ronson, Aharon, additional, Ruchlemer, Rosa, additional, de Deus Santos, Marcos Daniel, additional, Schipani, Mattia, additional, Schiwitza, Annett, additional, Shen, Yandong, additional, Simkovic, Martin, additional, Smirnova, Svetlana, additional, Sameh Abdelrahman Soliman, Dina, additional, Spacek, Martin, additional, Tadmor, Tamar, additional, Tomic, Kristina, additional, Tse, Eric, additional, Vassilakopoulos, Theodoros, additional, Visentin, Andrea, additional, Vitale, Candida, additional, Tresckow, Julia von, additional, Vrachiolias, George, additional, Vukovic, Vojin, additional, Walewska, Renata, additional, Wasik-Szczepanek, Ewa, additional, Xu, Zhenshu, additional, Yagci, Munci, additional, Yañez, Lucrecia, additional, Yassin, Mohamed, additional, Zuchnicka, Jana, additional, Angelopoulou, Maria, additional, Antic, Darko, additional, Biderman, Bella, additional, Catherwood, Mark, additional, Claus, Rainer, additional, Coscia, Marta, additional, Cuneo, Antonio, additional, Demirkan, Fatih, additional, Espinet, Blanca, additional, Gaidano, Gianluca, additional, Kalashnikova, Olga, additional, Laurenti, Luca, additional, Nikitin, Eugene, additional, Pangalis, Gerassimos A., additional, Panagiotidis, Panagiotis, additional, Mulligan, Stephen, additional, Popov, Viola Maria, additional, Pospisilova, Sarka, additional, Smolej, Lukas, additional, Sportoletti, Paolo, additional, Stavroyianni, Niki, additional, Tam, Constantine, additional, Trentin, Livio, additional, Chatzidimitriou, Anastasia, additional, Bosch, Francesc, additional, Doubek, Michael, additional, Ghia, Paolo, additional, and Stamatopoulos, Kostas, additional

Published
2023
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32. Concept and feasibility of the Augsburg Longitudinal Plasma Study (ALPS) – a prospective trial for comprehensive liquid biopsy-based longitudinal monitoring of solid cancer patients

Author

Sommer, Sebastian, Schmutz, Maximilian, Hildebrand, Kathrin, Schiwitza, Annett, Benedikt, Selinah, Eberle, Maria, Mögele, Tatiana, Sultan, Aziz, Reichl, Lena, Campillo, Maria, Uhrmacher, Luise, Nikolic, Ana Antic, Bundschuh, Ralph, Lapa, Constantin, Kuhlen, Michaela, Dintner, Sebastian, Langer, Angela, Märkl, Bruno, Wendler, Thomas, Tehlan, Kartikay, Kröncke, Thomas, Wahle, Maria, Mann, Matthias, Casadei, Nicolas, Pogoda, Michaela, Hummler, Simone, Sax, Irmengard, Schlesner, Matthias, Kubuschok, Boris, Trepel, Martin, and Claus, Rainer

Published
2024
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35. Sorafenib promotes graft-versus-leukemia activity in mice and humans through IL-15 production in FLT3-ITD-mutant leukemia cells

Author

Mathew, Nimitha R, Baumgartner, Francis, Braun, Lukas, O'Sullivan, David, Thomas, Simone, Waterhouse, Miguel, Müller, Tony A, Hanke, Kathrin, Taromi, Sanaz, Apostolova, Petya, Illert, Anna L, Melchinger, Wolfgang, Duquesne, Sandra, Schmitt-Graeff, Annette, Osswald, Lena, Yan, Kai-Li, Weber, Arnim, Tugues, Sonia, Spath, Sabine, Pfeifer, Dietmar, Follo, Marie, Claus, Rainer, Lübbert, Michael, Rummelt, Christoph, Bertz, Hartmut, Wäsch, Ralph, Haag, Johanna, Schmidts, Andrea, Schultheiss, Michael, Bettinger, Dominik, Thimme, Robert, Ullrich, Evelyn, Tanriver, Yakup, Vuong, Giang Lam, Arnold, Renate, Hemmati, Philipp, Wolf, Dominik, Ditschkowski, Markus, Jilg, Cordula, Wilhelm, Konrad, Leiber, Christian, Gerull, Sabine, Halter, Jörg, Lengerke, Claudia, Pabst, Thomas, Schroeder, Thomas, Kobbe, Guido, Rösler, Wolf, Doostkam, Soroush, Meckel, Stephan, Stabla, Kathleen, Metzelder, Stephan K, Halbach, Sebastian, Brummer, Tilman, Hu, Zehan, Dengjel, Joern, Hackanson, Björn, Schmid, Christoph, Holtick, Udo, Scheid, Christof, Spyridonidis, Alexandros, Stölzel, Friedrich, Ordemann, Rainer, Müller, Lutz P, Sicre-de-Fontbrune, Flore, Ihorst, Gabriele, Kuball, Jürgen, Ehlert, Jan E, Feger, Daniel, Wagner, Eva-Maria, Cahn, Jean-Yves, Schnell, Jacqueline, Kuchenbauer, Florian, Bunjes, Donald, Chakraverty, Ronjon, Richardson, Simon, Gill, Saar, Kröger, Nicolaus, Ayuk, Francis, Vago, Luca, Ciceri, Fabio, Müller, Antonia M, Kondo, Takeshi, Teshima, Takanori, Klaeger, Susan, Kuster, Bernhard, Weisdorf, Daniel, van der Velden, Walter, Dörfel, Daniela, Bethge, Wolfgang, Hilgendorf, Inken, Hochhaus, Andreas, Andrieux, Geoffroy, Börries, Melanie, Busch, Hauke, Magenau, John, Reddy, Pavan, Labopin, Myriam, Antin, Joseph H, Henden, Andrea S, Hill, Geoffrey R, Kennedy, Glen A, Bar, Merav, Sarma, Anita, McLornan, Donal, Mufti, Ghulam, Oran, Betul, Rezvani, Katayoun, Shah, Omid, Negrin, Robert S, Nagler, Arnon, Prinz, Marco, Burchert, Andreas, Neubauer, Andreas, Beelen, Dietrich, Mackensen, Andreas, von Bubnoff, Nikolas, Herr, Wolfgang, Becher, Burkhard, Socié, Gerard, Caligiuri, Michael A, Ruggiero, Eliana, Bonini, Chiara, Häcker, Georg, Duyster, Justus, Finke, Jürgen, Pearce, Erika, Blazar, Bruce R, and Zeiser, Robert

Subjects
Interleukin-15 -- Health aspects, Gene mutation -- Health aspects, Sorafenib -- Patient outcomes, Gene expression -- Health aspects, Acute myelocytic leukemia -- Genetic aspects -- Development and progression -- Drug therapy, Biological sciences, Health
Abstract

Individuals with acute myeloid leukemia (AML) harboring an internal tandem duplication (ITD) in the gene encoding Fms-related tyrosine kinase 3 (FLT3) who relapse after allogeneic hematopoietic cell transplantation (allo-HCT) have a 1-year survival rate below 20%. We observed that sorafenib, a multitargeted tyrosine kinase inhibitor, increased IL-15 production by FLT3-ITD[sup.+] leukemia cells. This synergized with the allogeneic CD8[sup.+] T cell response, leading to long-term survival in six mouse models of FLT3-ITD[sup.+] AML. Sorafenib-related IL-15 production caused an increase in CD8[sup.+]CD107a[sup.+]IFN-[gamma][sup.+] T cells with features of longevity (high levels of Bcl-2 and reduced PD-1 levels), which eradicated leukemia in secondary recipients. Mechanistically, sorafenib reduced expression of the transcription factor ATF4, thereby blocking negative regulation of interferon regulatory factor 7 (IRF7) activation, which enhanced IL-15 transcription. Both IRF7 knockdown and ATF4 overexpression in leukemia cells antagonized sorafenib-induced IL-15 production in vitro. Human FLT3-ITD[sup.+] AML cells obtained from sorafenib responders following sorafenib therapy showed increased levels of IL-15, phosphorylated IRF7, and a transcriptionally active IRF7 chromatin state. The mitochondrial spare respiratory capacity and glycolytic capacity of CD8[sup.+] T cells increased upon sorafenib treatment in sorafenib responders but not in nonresponders. Our findings indicate that the synergism of T cells and sorafenib is mediated via reduced ATF4 expression, causing activation of the IRF7-IL-15 axis in leukemia cells and thereby leading to metabolic reprogramming of leukemia-reactive T cells in humans. Therefore, sorafenib treatment has the potential to contribute to an immune-mediated cure of FLT3-ITD-mutant AML relapse, an otherwise fatal complication after allo-HCT., Author(s): Nimitha R Mathew [1, 2]; Francis Baumgartner [1]; Lukas Braun [1]; David O'Sullivan [3]; Simone Thomas [4]; Miguel Waterhouse [1]; Tony A Müller [1]; Kathrin Hanke [1, 2]; Sanaz [...]

Published
2018
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36. Data from Genome-wide DNA Methylation Events in TMPRSS2–ERG Fusion-Negative Prostate Cancers Implicate an EZH2-Dependent Mechanism with miR-26a Hypermethylation

Author

Börno, Stefan T., primary, Fischer, Axel, primary, Kerick, Martin, primary, Fälth, Maria, primary, Laible, Mark, primary, Brase, Jan C., primary, Kuner, Ruprecht, primary, Dahl, Andreas, primary, Grimm, Christina, primary, Sayanjali, Behnam, primary, Isau, Melanie, primary, Röhr, Christina, primary, Wunderlich, Andrea, primary, Timmermann, Bernd, primary, Claus, Rainer, primary, Plass, Christoph, primary, Graefen, Markus, primary, Simon, Ronald, primary, Demichelis, Francesca, primary, Rubin, Mark A., primary, Sauter, Guido, primary, Schlomm, Thorsten, primary, Sültmann, Holger, primary, Lehrach, Hans, primary, and Schweiger, Michal R., primary

Published
2023
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37. Supplementary Figure Legends 1-5, Table Legends 1-4 from Genome-wide DNA Methylation Events in TMPRSS2–ERG Fusion-Negative Prostate Cancers Implicate an EZH2-Dependent Mechanism with miR-26a Hypermethylation

Author

Börno, Stefan T., primary, Fischer, Axel, primary, Kerick, Martin, primary, Fälth, Maria, primary, Laible, Mark, primary, Brase, Jan C., primary, Kuner, Ruprecht, primary, Dahl, Andreas, primary, Grimm, Christina, primary, Sayanjali, Behnam, primary, Isau, Melanie, primary, Röhr, Christina, primary, Wunderlich, Andrea, primary, Timmermann, Bernd, primary, Claus, Rainer, primary, Plass, Christoph, primary, Graefen, Markus, primary, Simon, Ronald, primary, Demichelis, Francesca, primary, Rubin, Mark A., primary, Sauter, Guido, primary, Schlomm, Thorsten, primary, Sültmann, Holger, primary, Lehrach, Hans, primary, and Schweiger, Michal R., primary

Published
2023
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38. Supplementary Figures 1-5 from Genome-wide DNA Methylation Events in TMPRSS2–ERG Fusion-Negative Prostate Cancers Implicate an EZH2-Dependent Mechanism with miR-26a Hypermethylation

Author

Börno, Stefan T., primary, Fischer, Axel, primary, Kerick, Martin, primary, Fälth, Maria, primary, Laible, Mark, primary, Brase, Jan C., primary, Kuner, Ruprecht, primary, Dahl, Andreas, primary, Grimm, Christina, primary, Sayanjali, Behnam, primary, Isau, Melanie, primary, Röhr, Christina, primary, Wunderlich, Andrea, primary, Timmermann, Bernd, primary, Claus, Rainer, primary, Plass, Christoph, primary, Graefen, Markus, primary, Simon, Ronald, primary, Demichelis, Francesca, primary, Rubin, Mark A., primary, Sauter, Guido, primary, Schlomm, Thorsten, primary, Sültmann, Holger, primary, Lehrach, Hans, primary, and Schweiger, Michal R., primary

Published
2023
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39. Data from Evolution of DNA Methylation Is Linked to Genetic Aberrations in Chronic Lymphocytic Leukemia

Author

Oakes, Christopher C., primary, Claus, Rainer, primary, Gu, Lei, primary, Assenov, Yassen, primary, Hüllein, Jennifer, primary, Zucknick, Manuela, primary, Bieg, Matthias, primary, Brocks, David, primary, Bogatyrova, Olga, primary, Schmidt, Christopher R., primary, Rassenti, Laura, primary, Kipps, Thomas J., primary, Mertens, Daniel, primary, Lichter, Peter, primary, Döhner, Hartmut, primary, Stilgenbauer, Stephan, primary, Byrd, John C., primary, Zenz, Thorsten, primary, and Plass, Christoph, primary

Published
2023
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40. Supplementary Figures 1-10 from Evolution of DNA Methylation Is Linked to Genetic Aberrations in Chronic Lymphocytic Leukemia

Author

Oakes, Christopher C., primary, Claus, Rainer, primary, Gu, Lei, primary, Assenov, Yassen, primary, Hüllein, Jennifer, primary, Zucknick, Manuela, primary, Bieg, Matthias, primary, Brocks, David, primary, Bogatyrova, Olga, primary, Schmidt, Christopher R., primary, Rassenti, Laura, primary, Kipps, Thomas J., primary, Mertens, Daniel, primary, Lichter, Peter, primary, Döhner, Hartmut, primary, Stilgenbauer, Stephan, primary, Byrd, John C., primary, Zenz, Thorsten, primary, and Plass, Christoph, primary

Published
2023
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41. Supplementary Table 2 from Evolution of DNA Methylation Is Linked to Genetic Aberrations in Chronic Lymphocytic Leukemia

Author

Oakes, Christopher C., primary, Claus, Rainer, primary, Gu, Lei, primary, Assenov, Yassen, primary, Hüllein, Jennifer, primary, Zucknick, Manuela, primary, Bieg, Matthias, primary, Brocks, David, primary, Bogatyrova, Olga, primary, Schmidt, Christopher R., primary, Rassenti, Laura, primary, Kipps, Thomas J., primary, Mertens, Daniel, primary, Lichter, Peter, primary, Döhner, Hartmut, primary, Stilgenbauer, Stephan, primary, Byrd, John C., primary, Zenz, Thorsten, primary, and Plass, Christoph, primary

Published
2023
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42. Supplementary Table 1 from Evolution of DNA Methylation Is Linked to Genetic Aberrations in Chronic Lymphocytic Leukemia

Author

Oakes, Christopher C., primary, Claus, Rainer, primary, Gu, Lei, primary, Assenov, Yassen, primary, Hüllein, Jennifer, primary, Zucknick, Manuela, primary, Bieg, Matthias, primary, Brocks, David, primary, Bogatyrova, Olga, primary, Schmidt, Christopher R., primary, Rassenti, Laura, primary, Kipps, Thomas J., primary, Mertens, Daniel, primary, Lichter, Peter, primary, Döhner, Hartmut, primary, Stilgenbauer, Stephan, primary, Byrd, John C., primary, Zenz, Thorsten, primary, and Plass, Christoph, primary

Published
2023
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43. Supplementary Tables 1-4 from Genome-wide DNA Methylation Events in TMPRSS2–ERG Fusion-Negative Prostate Cancers Implicate an EZH2-Dependent Mechanism with miR-26a Hypermethylation

Author

Börno, Stefan T., primary, Fischer, Axel, primary, Kerick, Martin, primary, Fälth, Maria, primary, Laible, Mark, primary, Brase, Jan C., primary, Kuner, Ruprecht, primary, Dahl, Andreas, primary, Grimm, Christina, primary, Sayanjali, Behnam, primary, Isau, Melanie, primary, Röhr, Christina, primary, Wunderlich, Andrea, primary, Timmermann, Bernd, primary, Claus, Rainer, primary, Plass, Christoph, primary, Graefen, Markus, primary, Simon, Ronald, primary, Demichelis, Francesca, primary, Rubin, Mark A., primary, Sauter, Guido, primary, Schlomm, Thorsten, primary, Sültmann, Holger, primary, Lehrach, Hans, primary, and Schweiger, Michal R., primary

Published
2023
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44. Other malignancies in the history of CLL: an international multicenter study conducted by ERIC, the European Research Initiative on CLL, in HARMONY

Author

AbbVie Pharmaceuticals, European Commission, Chatzikonstantinou, Thomas, Scarfò, Lydia, Karakatsoulis, Georgios, Minga, Eva, Chamou, Dimitra, Iacoboni, Gloria, Kotaskova, Jana, Demosthenous, Christos, Smolej, Lukas, Mulligan, Stephen, Alcoceba, Miguel, Kreitman, Robert J., Labrador, Jorge, Lad, Deepesh, Levin, Mark-David, Levy, Ilana, Longval, Thomas, López-García, Alberto, Marquet, Juan, Martín-Rodríguez, Lucía, Maynadié, Marc, Tadmor, Tamar, Maslejova, Stanislava, Mayor-Bastida, Carlota, Mihaljevic, Biljana, Milosevic, Ivana, Mirás, Fátima, Moia, Riccardo, Morawska, Marta, Murru, Roberta, Nath, Uttam Kumar, Navarro-Bailón, Almudena, Tomic, Kristina, Oliveira, Ana C., Olivieri, Jacopo, Oscier, David, Panovska-Stavridis, Irina, Papaioannou, María, Papajík, Tomás, Kubova, Zuzana, Phumphukhieo, Punyarat, Pierie, Cheyenne, Puiggros, Anna, Tse, Eric, Rani, Lata, Reda, Gianluigi, Rigolin, Gian Matteo, Ruchlemer, Rosa, Daniel de Deus Santos, Marcos, Schipani, Mattia, Schiwitza, Annett, Shen, Yandong, Simkovic, Martín, Smirnova, Svetlana, Vassilakopoulos, Theodoros, Abdelrahman Soliman, Dina Sameh, Spacek, Martin, Visentin, Andrea, Vitale, Candida, von Tresckow, Julia, Vrachiolias, George, Vukovic, Vojin, Walewska, Renata, Al-Shemari, Salem, Wasik-Szczepanek, Ewa, Xu, Zhenshu, Yagci, Munci, Yañez, Lucrecia, Yassin, Mohamed, Zuchnicka, Jana, Angelopoulou, Maria, Antic, Darko, Biderman, Bella, Catherwood, Mark, Aurran-Schleinitz, Thérèse, Claus, Rainer, Coscia, Marta, Cuneo, Antonio, Demirkan, Fatih, Espinet, Blanca, Gaidano, Gianluca, Kalashnikova, Olga B., Laurenti, Luca, Nikitin, Eugene, Pangalis, Gerassimos A., Bacchiarri, Francesca, Panagiotidis, Panagiotis, Popov, Viola María, Pospisilova, Sarka, Sportoletti, Paolo, Stavroyianni, Niki, Tam, Constantine S., Trentin, Livio, Chatzidimitriou, Anastasia, Bosch, Francesc, Doubek, Michael, Bellido, Mar, Ghia, Paolo, Stamatopoulos, Kostas, Bijou, Fontanet, Calleja, Anne, Medina, Angeles, Khan, Mehreen Ali, Cassin, Ramona, Chatzileontiadou, Sofía, Collado, Rosa, Christian, Amy, Davis, Zadie, Dimou, María, Donaldson, David, Santos, Gimena Dos, Dreta, Bárbara, Efstathopoulou, María, El-Ashwah, Shaimaa, Enrico, Alicia, Fresa, Alberto, Galimberti, Sara, Galitzia, Andrea, García-Serra, Rocío, Gimeno, Eva, González-Gascón y Marín, Isabel, Gozzetti, Alessandro, Guarente, Valerio, Guieze, Romain, Gogia, Ajay, Gupta, Ritu, Harrop, Sean, Hatzimichael, Eleftheria, Herishanu, Yair, Hernández-Rivas, José Ángel, Inchiappa, Luca, Jaksic, Ozren, Janssen, Susanne, Kalicińska, Elżbieta, Kamel, Laribi, Karakus, Volkan, Kater, Arnon P., Kho, Bonnie, Kislova, María, Konstantinou, Eliana, Koren-Michowitz, Maya, Kotsianidis, Ioannis, AbbVie Pharmaceuticals, European Commission, Chatzikonstantinou, Thomas, Scarfò, Lydia, Karakatsoulis, Georgios, Minga, Eva, Chamou, Dimitra, Iacoboni, Gloria, Kotaskova, Jana, Demosthenous, Christos, Smolej, Lukas, Mulligan, Stephen, Alcoceba, Miguel, Kreitman, Robert J., Labrador, Jorge, Lad, Deepesh, Levin, Mark-David, Levy, Ilana, Longval, Thomas, López-García, Alberto, Marquet, Juan, Martín-Rodríguez, Lucía, Maynadié, Marc, Tadmor, Tamar, Maslejova, Stanislava, Mayor-Bastida, Carlota, Mihaljevic, Biljana, Milosevic, Ivana, Mirás, Fátima, Moia, Riccardo, Morawska, Marta, Murru, Roberta, Nath, Uttam Kumar, Navarro-Bailón, Almudena, Tomic, Kristina, Oliveira, Ana C., Olivieri, Jacopo, Oscier, David, Panovska-Stavridis, Irina, Papaioannou, María, Papajík, Tomás, Kubova, Zuzana, Phumphukhieo, Punyarat, Pierie, Cheyenne, Puiggros, Anna, Tse, Eric, Rani, Lata, Reda, Gianluigi, Rigolin, Gian Matteo, Ruchlemer, Rosa, Daniel de Deus Santos, Marcos, Schipani, Mattia, Schiwitza, Annett, Shen, Yandong, Simkovic, Martín, Smirnova, Svetlana, Vassilakopoulos, Theodoros, Abdelrahman Soliman, Dina Sameh, Spacek, Martin, Visentin, Andrea, Vitale, Candida, von Tresckow, Julia, Vrachiolias, George, Vukovic, Vojin, Walewska, Renata, Al-Shemari, Salem, Wasik-Szczepanek, Ewa, Xu, Zhenshu, Yagci, Munci, Yañez, Lucrecia, Yassin, Mohamed, Zuchnicka, Jana, Angelopoulou, Maria, Antic, Darko, Biderman, Bella, Catherwood, Mark, Aurran-Schleinitz, Thérèse, Claus, Rainer, Coscia, Marta, Cuneo, Antonio, Demirkan, Fatih, Espinet, Blanca, Gaidano, Gianluca, Kalashnikova, Olga B., Laurenti, Luca, Nikitin, Eugene, Pangalis, Gerassimos A., Bacchiarri, Francesca, Panagiotidis, Panagiotis, Popov, Viola María, Pospisilova, Sarka, Sportoletti, Paolo, Stavroyianni, Niki, Tam, Constantine S., Trentin, Livio, Chatzidimitriou, Anastasia, Bosch, Francesc, Doubek, Michael, Bellido, Mar, Ghia, Paolo, Stamatopoulos, Kostas, Bijou, Fontanet, Calleja, Anne, Medina, Angeles, Khan, Mehreen Ali, Cassin, Ramona, Chatzileontiadou, Sofía, Collado, Rosa, Christian, Amy, Davis, Zadie, Dimou, María, Donaldson, David, Santos, Gimena Dos, Dreta, Bárbara, Efstathopoulou, María, El-Ashwah, Shaimaa, Enrico, Alicia, Fresa, Alberto, Galimberti, Sara, Galitzia, Andrea, García-Serra, Rocío, Gimeno, Eva, González-Gascón y Marín, Isabel, Gozzetti, Alessandro, Guarente, Valerio, Guieze, Romain, Gogia, Ajay, Gupta, Ritu, Harrop, Sean, Hatzimichael, Eleftheria, Herishanu, Yair, Hernández-Rivas, José Ángel, Inchiappa, Luca, Jaksic, Ozren, Janssen, Susanne, Kalicińska, Elżbieta, Kamel, Laribi, Karakus, Volkan, Kater, Arnon P., Kho, Bonnie, Kislova, María, Konstantinou, Eliana, Koren-Michowitz, Maya, and Kotsianidis, Ioannis

Abstract

[Background]: Patients with chronic lymphocytic leukemia (CLL) have a higher risk of developing other malignancies (OMs) compared to the general population. However, the impact of CLL-related risk factors and CLL-directed treatment is still unclear and represents the focus of this work., [Methods]: We conducted a retrospective international multicenter study to assess the incidence of OMs and detect potential risk factors in 19,705 patients with CLL, small lymphocytic lymphoma, or high-count CLL-like monoclonal B-cell lymphocytosis, diagnosed between 2000 and 2016. Data collection took place between October 2020 and March 2022., [Findings]: In 129,254 years of follow-up after CLL diagnosis, 3513 OMs were diagnosed (27.2 OMs/1000 person-years). The most common hematological OMs were Richter transformation, myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Non-melanoma skin (NMSC) and prostate cancers were the most common solid tumors (STs). The only predictor for MDS and AML development was treatment with fludarabine and cyclophosphamide with/without rituximab (FC ± R) (OR = 3.7; 95% CI = 2.79–4.91; p < 0.001). STs were more frequent in males and patients with unmutated immunoglobulin heavy variable genes (OR = 1.77; 95% CI = 1.49–2.11; p < 0.001/OR = 1.89; 95% CI = 1.6–2.24; p < 0.001). CLL-directed treatment was associated with non-melanoma skin and prostate cancers (OR = 1.8; 95% CI = 1.36–2.41; p < 0.001/OR = 2.11; 95% CI = 1.12–3.97; p = 0.021). In contrast, breast cancers were more frequent in untreated patients (OR = 0.17; 95% CI = 0.08–0.33; p < 0.001). Patients with CLL and an OM had inferior overall survival (OS) than those without. AML and MDS conferred the worst OS (p < 0.001)., [Interpretation]: OMs in CLL impact on OS. Treatment for CLL increased the risk for AML/MDS, prostate cancer, and NMSC. FCR was associated with increased risk for AML/MDS.

Published
2023

48. Supplementary Table 6 from Extensive Promoter DNA Hypermethylation and Hypomethylation Is Associated with Aberrant MicroRNA Expression in Chronic Lymphocytic Leukemia

Author

Baer, Constance, primary, Claus, Rainer, primary, Frenzel, Lukas P., primary, Zucknick, Manuela, primary, Park, Yoon Jung, primary, Gu, Lei, primary, Weichenhan, Dieter, primary, Fischer, Martina, primary, Pallasch, Christian Philipp, primary, Herpel, Esther, primary, Rehli, Michael, primary, Byrd, John C., primary, Wendtner, Clemens-Martin, primary, and Plass, Christoph, primary

Published
2023
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49. Supplementary Table 2 from Extensive Promoter DNA Hypermethylation and Hypomethylation Is Associated with Aberrant MicroRNA Expression in Chronic Lymphocytic Leukemia

Author

Baer, Constance, primary, Claus, Rainer, primary, Frenzel, Lukas P., primary, Zucknick, Manuela, primary, Park, Yoon Jung, primary, Gu, Lei, primary, Weichenhan, Dieter, primary, Fischer, Martina, primary, Pallasch, Christian Philipp, primary, Herpel, Esther, primary, Rehli, Michael, primary, Byrd, John C., primary, Wendtner, Clemens-Martin, primary, and Plass, Christoph, primary

Published
2023
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50. Supplementary Table 4 from Extensive Promoter DNA Hypermethylation and Hypomethylation Is Associated with Aberrant MicroRNA Expression in Chronic Lymphocytic Leukemia

Author

Baer, Constance, primary, Claus, Rainer, primary, Frenzel, Lukas P., primary, Zucknick, Manuela, primary, Park, Yoon Jung, primary, Gu, Lei, primary, Weichenhan, Dieter, primary, Fischer, Martina, primary, Pallasch, Christian Philipp, primary, Herpel, Esther, primary, Rehli, Michael, primary, Byrd, John C., primary, Wendtner, Clemens-Martin, primary, and Plass, Christoph, primary

Published
2023
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