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244 results on '"Kraemer, Alwin"'

1. Molecularly guided therapy versus chemotherapy after disease control in unfavourable cancer of unknown primary (CUPISCO): an open-label, randomised, phase 2 study

Author

Krämer, Alwin, Bochtler, Tilmann, Pauli, Chantal, Shiu, Kai-Keen, Cook, Natalie, de Menezes, Juliana Janoski, Pazo-Cid, Roberto A, Losa, Ferran, Robbrecht, Debbie GJ, Tomášek, Jiří, Arslan, Cagatay, Özgüroğlu, Mustafa, Stahl, Michael, Bigot, Frédéric, Kim, Sun Young, Naito, Yoichi, Italiano, Antoine, Chalabi, Nasséra, Durán-Pacheco, Gonzalo, Michaud, Chantal, Scarato, Jeremy, Thomas, Marlene, Ross, Jeffrey S, Moch, Holger, and Mileshkin, Linda

Published
2024
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3. Somatic mutational landscape of hereditary hematopoietic malignancies caused by germline variants in RUNX1, GATA2, and DDX41

Author

Homan, Claire C., Drazer, Michael W., Yu, Kai, Lawrence, David M., Feng, Jinghua, Arriola-Martinez, Luis, Pozsgai, Matthew J., McNeely, Kelsey E., Ha, Thuong, Venugopal, Parvathy, Arts, Peer, King-Smith, Sarah L., Cheah, Jesse, Armstrong, Mark, Wang, Paul, Bödör, Csaba, Cantor, Alan B., Cazzola, Mario, Degelman, Erin, DiNardo, Courtney D., Duployez, Nicolas, Favier, Remi, Fröhling, Stefan, Rio-Machin, Ana, Klco, Jeffery M., Krämer, Alwin, Kurokawa, Mineo, Lee, Joanne, Malcovati, Luca, Morgan, Neil V., Natsoulis, Georges, Owen, Carolyn, Patel, Keyur P., Preudhomme, Claude, Raslova, Hana, Rienhoff, Hugh, Ripperger, Tim, Schulte, Rachael, Tawana, Kiran, Velloso, Elvira, Yan, Benedict, Kim, Erika, Sood, Raman, Hsu, Amy P., Holland, Steven M., Phillips, Kerry, Poplawski, Nicola K., Babic, Milena, Wei, Andrew H., Forsyth, Cecily, Mar Fan, Helen, Lewis, Ian D., Cooney, Julian, Susman, Rachel, Fox, Lucy C., Blombery, Piers, Singhal, Deepak, Hiwase, Devendra, Phipson, Belinda, Schreiber, Andreas W., Hahn, Christopher N., Scott, Hamish S., Liu, Paul, Godley, Lucy A., and Brown, Anna L.

Published
2023
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4. Synthetic patches, real images: screening for centrosome aberrations in EM images of human cancer cells

Author

Lukoyanov, Artem, Haberbosch, Isabella, Pape, Constantin, Kraemer, Alwin, Schwab, Yannick, and Kreshuk, Anna

Subjects
Computer Science - Computer Vision and Pattern Recognition
Abstract

Recent advances in high-throughput electron microscopy imaging enable detailed study of centrosome aberrations in cancer cells. While the image acquisition in such pipelines is automated, manual detection of centrioles is still necessary to select cells for re-imaging at higher magnification. In this contribution we propose an algorithm which performs this step automatically and with high accuracy. From the image labels produced by human experts and a 3D model of a centriole we construct an additional training set with patch-level labels. A two-level DenseNet is trained on the hybrid training data with synthetic patches and real images, achieving much better results on real patient data than training only at the image-level. The code can be found at https://github.com/kreshuklab/centriole_detection., Comment: Accepted at MICCAI 2019

Published
2019

5. Differential impact of IDH1/2 mutational subclasses on outcome in adult AML: results from a large multicenter study

Author

Middeke, Jan M., Metzeler, Klaus H., Röllig, Christoph, Krämer, Michael, Eckardt, Jan-Niklas, Stasik, Sebastian, Greif, Philipp A., Spiekermann, Karsten, Rothenberg-Thurley, Maja, Krug, Utz, Braess, Jan, Krämer, Alwin, Hochhaus, Andreas, Brümmendorf, Tim H., Naumann, Ralph, Steffen, Björn, Einsele, Hermann, Schaich, Markus, Burchert, Andreas, Neubauer, Andreas, Görlich, Dennis, Sauerland, Cristina, Schäfer-Eckart, Kerstin, Schliemann, Christoph, Krause, Stefan W., Hänel, Mathias, Frickhofen, Norbert, Noppeney, Richard, Kaiser, Ulrich, Kaufmann, Martin, Kunadt, Desiree, Wörmann, Bernhard, Sockel, Katja, von Bonin, Malte, Herold, Tobias, Müller-Tidow, Carsten, Platzbecker, Uwe, Berdel, Wolfgang E., Serve, Hubert, Baldus, Claudia D., Ehninger, Gerhard, Schetelig, Johannes, Hiddemann, Wolfgang, Bornhäuser, Martin, Stölzel, Friedrich, and Thiede, Christian

Published
2022
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6. CEBPA mutations in 4708 patients with acute myeloid leukemia: differential impact of bZIP and TAD mutations on outcome

Author

Taube, Franziska, Georgi, Julia Annabell, Kramer, Michael, Stasik, Sebastian, Middeke, Jan Moritz, Röllig, Christoph, Krug, Utz, Krämer, Alwin, Scholl, Sebastian, Hochhaus, Andreas, Brümmendorf, Tim H., Naumann, Ralph, Petzold, Andreas, Mulet-Lazaro, Roger, Valk, Peter J.M., Steffen, Björn, Einsele, Hermann, Schaich, Markus, Burchert, Andreas, Neubauer, Andreas, Schäfer-Eckart, Kerstin, Schliemann, Christoph, Krause, Stefan W., Hänel, Mathias, Noppeney, Richard, Kaiser, Ulrich, Baldus, Claudia D., Kaufmann, Martin, Herold, Sylvia, Stölzel, Friedrich, Sockel, Katja, von Bonin, Malte, Müller-Tidow, Carsten, Platzbecker, Uwe, Berdel, Wolfgang E., Serve, Hubert, Ehninger, Gerhard, Bornhäuser, Martin, Schetelig, Johannes, and Thiede, Christian

Published
2022
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8. Impact of PTPN11 mutations on clinical outcome analyzed in 1529 patients with acute myeloid leukemia

Author

Stasik, Sebastian, Eckardt, Jan-Niklas, Kramer, Michael, Röllig, Christoph, Krämer, Alwin, Scholl, Sebastian, Hochhaus, Andreas, Crysandt, Martina, Brümmendorf, Tim H., Naumann, Ralph, Steffen, Björn, Kunzmann, Volker, Einsele, Hermann, Schaich, Markus, Burchert, Andreas, Neubauer, Andreas, Schäfer-Eckart, Kerstin, Schliemann, Christoph, Krause, Stefan, Herbst, Regina, Hänel, Mathias, Frickhofen, Norbert, Noppeney, Richard, Kaiser, Ulrich, Baldus, Claudia D., Kaufmann, Martin, Rácil, Zdenek, Platzbecker, Uwe, Berdel, Wolfgang E., Mayer, Jiri, Serve, Hubert, Müller-Tidow, Carsten, Ehninger, Gerhard, Bornhäuser, Martin, Schetelig, Johannes, Middeke, Jan M., and Thiede, Christian

Published
2021
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9. Clinical Outcomes in Patients with FLT3-ITD-Mutated Relapsed/Refractory Acute Myelogenous Leukemia Undergoing Hematopoietic Stem Cell Transplantation after Quizartinib or Salvage Chemotherapy in the QuANTUM-R Trial

Author

Ganguly, Siddhartha, Cortes, Jorge E., Krämer, Alwin, Levis, Mark J., Martinelli, Giovanni, Perl, Alexander E., Russell, Nigel H., Arunachalam, Meena, Santos, Cedric Dos, Gammon, Guy, Lesegretain, Arnaud, Mires, Derek E., Pham, Hoang, Wang, Yibin, and Khaled, Samer K.

Published
2021
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10. STIL overexpression shortens lifespan and reduces tumor formation in mice

Author

Moussa, Amira Talaat, primary, Cosenza, Marco R, additional, Wohlfromm, Timothy, additional, Brobeil, Katharina, additional, Hill, Anthony, additional, Patrizi, Annarita, additional, Mueller-Decker, Karin, additional, Holland-Letz, Tim, additional, Jauch, Anna, additional, Kraft, Bianca, additional, and Kraemer, Alwin, additional

Published
2023
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11. Enasidenib

Author

Krämer, Alwin, Bochtler, Tilmann, Schlag, Peter-Michael, Series Editor, Senn, Hans-Jörg, Series Editor, and Martens, Uwe M., editor

Published
2018
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12. Quizartinib versus salvage chemotherapy in relapsed or refractory FLT3-ITD acute myeloid leukaemia (QuANTUM-R): a multicentre, randomised, controlled, open-label, phase 3 trial

Author

Cortes, Jorge E, Khaled, Samer, Martinelli, Giovanni, Perl, Alexander E, Ganguly, Siddhartha, Russell, Nigel, Krämer, Alwin, Dombret, Hervé, Hogge, Donna, Jonas, Brian A, Leung, Anskar Yu-Hung, Mehta, Priyanka, Montesinos, Pau, Radsak, Markus, Sica, Simona, Arunachalam, Meena, Holmes, Melissa, Kobayashi, Ken, Namuyinga, Ruth, Ge, Nanxiang, Yver, Antoine, Zhang, Yufen, and Levis, Mark J

Published
2019
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17. Introduction

Author

Löffler, Harald, Krämer, Alwin, Krämer, Alwin, editor, and Löffler, Harald, editor

Published
2016
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19. Marker chromosomes can arise from chromothripsis and predict adverse prognosis in acute myeloid leukemia

Author

Bochtler, Tilmann, Granzow, Martin, Stölzel, Friedrich, Kunz, Christina, Mohr, Brigitte, Kartal-Kaess, Mutlu, Hinderhofer, Katrin, Heilig, Christoph E., Kramer, Michael, Thiede, Christian, Endris, Volker, Kirchner, Martina, Stenzinger, Albrecht, Benner, Axel, Bornhäuser, Martin, Ehninger, Gerhard, Ho, Anthony D., Jauch, Anna, and Krämer, Alwin

Published
2017
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20. A phase 1 study of IDH305 in patients with IDH1(R132)-mutant acute myeloid leukemia or myelodysplastic syndrome

Author

DiNardo, Courtney D., Hochhaus, Andreas, Frattini, Mark G., Yee, Karen, Zander, Thomas, Kraemer, Alwin, Chen, Xueying, Ji, Yan, Parikh, Nehal S., Choi, Joanne, Wei, Andrew H., DiNardo, Courtney D., Hochhaus, Andreas, Frattini, Mark G., Yee, Karen, Zander, Thomas, Kraemer, Alwin, Chen, Xueying, Ji, Yan, Parikh, Nehal S., Choi, Joanne, and Wei, Andrew H.

Abstract

Purpose Isocitrate dehydrogenase enzyme 1 (IDH1) mutations at 132nd amino acid residue (R132*) result in the cellular accumulation of the oncometabolite, 2-hydroxyglutarate (2-HG). IDH305 is an orally bioavailable, brain-penetrant, mutant-selective allosteric IDH1 inhibitor demonstrating target engagement in preclinical models. This first-in human study was designed to identify the recommended dose for expansion/maximum tolerated dose of IDH305 in patients with IDH1(R132)-mutant acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Methods IDH305 was given at doses 75-750 mg twice daily in 41 patients with IDH1(R132)-mutant AML/MDS. Dose escalation was designed using Bayesian hierarchical model with overdose control principle and relationship with dose-limiting toxicity. Results IDH305 exhibited rapid absorption with mean T-1/2 approximately 4-10 h across doses. Interpatient variability was moderate and exposure increased with dose in a less than dose proportional manner. Most patients (35/41) demonstrated target engagement with reduction in 2-HG concentration at all doses. Complete remission (CR) or CR with incomplete count recovery occurred in 10/37 (27%) patients with AML and 1/ 4 patients with MDS. Adverse events (AEs) suspected to be related to study drug were reported in 53.7% of patients: increased blood bilirubin (14.6%), nausea (14.6%), increased alanine aminotransferase and aspartate aminotransferase (12.2%, each); most frequent grade 3 or 4 AEs were differentiation syndrome and tumor lysis syndrome (n = 3; 7.3%, each). Hepatotoxicity was manageable with dose modification. Conclusion Due to potentially narrow therapeutic window, the study was prematurely halted and recommended phase 2 dose could not be declared.

Published
2023

21. Addition of sorafenib versus placebo to standard therapy in patients aged 60 years or younger with newly diagnosed acute myeloid leukaemia (SORAML): a multicentre, phase 2, randomised controlled trial

Author

Röllig, Christoph, Serve, Hubert, Hüttmann, Andreas, Noppeney, Richard, Müller-Tidow, Carsten, Krug, Utz, Baldus, Claudia D, Brandts, Christian H, Kunzmann, Volker, Einsele, Hermann, Krämer, Alwin, Schäfer-Eckart, Kerstin, Neubauer, Andreas, Burchert, Andreas, Giagounidis, Aristoteles, Krause, Stefan W, Mackensen, Andreas, Aulitzky, Walter, Herbst, Regina, Hänel, Mathias, Kiani, Alexander, Frickhofen, Norbert, Kullmer, Johannes, Kaiser, Ulrich, Link, Hartmut, Geer, Thomas, Reichle, Albert, Junghanß, Christian, Repp, Roland, Heits, Frank, Dürk, Heinz, Hase, Jana, Klut, Ina-Maria, Illmer, Thomas, Bornhäuser, Martin, Schaich, Markus, Parmentier, Stefani, Görner, Martin, Thiede, Christian, von Bonin, Malte, Schetelig, Johannes, Kramer, Michael, Berdel, Wolfgang E, and Ehninger, Gerhard

Published
2015
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23. Randomized, phase 2 trial of low-dose cytarabine with or without volasertib in AML patients not suitable for induction therapy

Author

Döhner, Hartmut, Lübbert, Michael, Fiedler, Walter, Fouillard, Loic, Haaland, Alf, Brandwein, Joseph M., Lepretre, Stephane, Reman, Oumedaly, Turlure, Pascal, Ottmann, Oliver G., Müller-Tidow, Carsten, Krämer, Alwin, Raffoux, Emmanuel, Döhner, Konstanze, Schlenk, Richard F., Voss, Florian, Taube, Tillmann, Fritsch, Holger, and Maertens, Johan

Published
2014
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27. Somatic Mutational Landscape of Hereditary Hematopoietic Malignancies Associated with Germline Variants in RUNX1, GATA2 and DDX41

Author

Brown, Anna L., Homan, Claire, Drazer, Michael W., Yu, Kai, Lawrence, David, Feng, Jinghua, Arriola-Martinez, Luis, Pozsgai, Matthew, McNeely, Kelsey, Ha, Thuong, Venugopal, Parvathy, Arts, Peer, King-Smith, Sarah, Cheah, Jesse JC, Armstrong, Mark, Bödör, Csaba, Wang, Paul, Cantor, Alan B., Cazzola, Mario, Degelman, Erin, DiNardo, Courtney D., Duployez, Nicolas, Favier, Remi, Fröhling, Stefan, Rio-Machin, Ana, Klco, Jeffery M., Krämer, Alwin, Kurokawa, Mineo, Lee, Joanne, Malcovati, Luca, Morgan, Neil V, Natsoulis, Georges, Owen, Carolyn, Patel, Keyur P., Preudhomme, Claude, Raslova, Hana, Rienhoff, Hugh Young, Jr., Ripperger, Tim, Schulte, Rachael, Tawana, Kiran, Velloso, Elvira Deolinda Rodrigues Pereira, Yan, Benedict, Sood, Raman, Hsu, Amy, Holland, Steven M., Phillips, Kerry, Poplawski, Nicola, Babic, Milena, Kwon Kim, Erika M, Wei, Andrew H., Forsyth, Cecily, Mar Fan, Helen, Lewis, Ian D, Cooney, Julian, Susman, Rachel, Fox, Lucy C, Blombery, Piers, Singhal, Deepak, Hiwase, Devendra, Schreiber, Andreas W, Hahn, Christopher N, Scott, Hamish S, Liu, Paul P., and Godley, Lucy A.

Published
2022
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29. Severe Dysbiosis and Specific Haemophilus and Neisseria Signatures as Hallmarks of the Oropharyngeal Microbiome in Critically Ill Coronavirus Disease 2019 (COVID-19) Patients

Author

de Castilhos, Juliana, Zamir, Eli, Hippchen, Theresa, Rohrbach, Roman, Schmidt, Sabine, Hengler, Silvana, Schumacher, Hanna, Neubauer, Melanie, Kunz, Sabrina, Mueller-Esch, Tonia, Hiergeist, Andreas, Gessner, Andre, Khalid, Dina, Gaiser, Rogier, Cullin, Nyssa, Papagiannarou, Stamatia M., Beuthien-Baumann, Bettina, Kraemer, Alwin, Bartenschlager, Ralf, Jaeger, Dirk, Mueller, Michael, Herth, Felix, Duerschmied, Daniel, Schneider, Jochen, Schmid, Roland M., Eberhardt, Johann F., Khodamoradi, Yascha, Vehreschild, Maria J. G. T., Teufel, Andreas, Ebert, Matthias P., Hau, Peter, Salzberger, Bernd, Schnitzler, Paul, Poeck, Hendrik, Elinav, Eran, Merle, Uta, Stein-Thoeringer, Christoph K., de Castilhos, Juliana, Zamir, Eli, Hippchen, Theresa, Rohrbach, Roman, Schmidt, Sabine, Hengler, Silvana, Schumacher, Hanna, Neubauer, Melanie, Kunz, Sabrina, Mueller-Esch, Tonia, Hiergeist, Andreas, Gessner, Andre, Khalid, Dina, Gaiser, Rogier, Cullin, Nyssa, Papagiannarou, Stamatia M., Beuthien-Baumann, Bettina, Kraemer, Alwin, Bartenschlager, Ralf, Jaeger, Dirk, Mueller, Michael, Herth, Felix, Duerschmied, Daniel, Schneider, Jochen, Schmid, Roland M., Eberhardt, Johann F., Khodamoradi, Yascha, Vehreschild, Maria J. G. T., Teufel, Andreas, Ebert, Matthias P., Hau, Peter, Salzberger, Bernd, Schnitzler, Paul, Poeck, Hendrik, Elinav, Eran, Merle, Uta, and Stein-Thoeringer, Christoph K.

Abstract

Background At the entry site of respiratory virus infections, the oropharyngeal microbiome has been proposed as a major hub integrating viral and host immune signals. Early studies suggested that infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are associated with changes of the upper and lower airway microbiome, and that specific microbial signatures may predict coronavirus disease 2019 (COVID-19) illness. However, the results are not conclusive, as critical illness can drastically alter a patient's microbiome through multiple confounders. Methods To study oropharyngeal microbiome profiles in SARS-CoV-2 infection, clinical confounders, and prediction models in COVID-19, we performed a multicenter, cross-sectional clinical study analyzing oropharyngeal microbial metagenomes in healthy adults, patients with non-SARS-CoV-2 infections, or with mild, moderate, and severe COVID-19 (n = 322 participants). Results In contrast to mild infections, patients admitted to a hospital with moderate or severe COVID-19 showed dysbiotic microbial configurations, which were significantly pronounced in patients treated with broad-spectrum antibiotics, receiving invasive mechanical ventilation, or when sampling was performed during prolonged hospitalization. In contrast, specimens collected early after admission allowed us to segregate microbiome features predictive of hospital COVID-19 mortality utilizing machine learning models. Taxonomic signatures were found to perform better than models utilizing clinical variables with Neisseria and Haemophilus species abundances as most important features. Conclusions In addition to the infection per se, several factors shape the oropharyngeal microbiome of severely affected COVID-19 patients and deserve consideration in the interpretation of the role of the microbiome in severe COVID-19. Nevertheless, we were able to extract microbial features that can help to predict clinical outcomes. Coronavirus disease 2019 (COVID

Published
2022

30. Severe Dysbiosis and Specific Haemophilus and Neisseria Signatures as Hallmarks of the Oropharyngeal Microbiome in Critically Ill Coronavirus Disease 2019 (COVID-19) Patients (ciab902, 2021)

Author

de Castilhos, Juliana, Zamir, Eli, Hippchen, Theresa, Rohrbach, Roman, Schmidt, Sabine, Hengler, Silvana, Schumacher, Hanna, Neubauer, Melanie, Kunz, Sabrina, Mueller-Esch, Tonia, Hiergeist, Andreas, Gessner, Andre, Khalid, Dina, Gaiser, Rogier, Cullin, Nyssa, Papagiannarou, Stamatia M., Beuthien-Baumann, Bettina, Kraemer, Alwin, Bartenschlager, Ralf, Jaeger, Dirk, Mueller, Michael, Herth, Felix, Duerschmied, Daniel, Schneider, Jochen, Schmid, Roland M., Eberhardt, Johann F., Khodamoradi, Yascha, Vehreschild, Maria J. G. T., Teufel, Andreas, Ebert, Matthias P., Hau, Peter, Salzberger, Bernd, Schnitzler, Paul, Poeck, Hendrik, Elinav, Eran, Merle, Uta, Stein-Thoeringer, Christoph K., de Castilhos, Juliana, Zamir, Eli, Hippchen, Theresa, Rohrbach, Roman, Schmidt, Sabine, Hengler, Silvana, Schumacher, Hanna, Neubauer, Melanie, Kunz, Sabrina, Mueller-Esch, Tonia, Hiergeist, Andreas, Gessner, Andre, Khalid, Dina, Gaiser, Rogier, Cullin, Nyssa, Papagiannarou, Stamatia M., Beuthien-Baumann, Bettina, Kraemer, Alwin, Bartenschlager, Ralf, Jaeger, Dirk, Mueller, Michael, Herth, Felix, Duerschmied, Daniel, Schneider, Jochen, Schmid, Roland M., Eberhardt, Johann F., Khodamoradi, Yascha, Vehreschild, Maria J. G. T., Teufel, Andreas, Ebert, Matthias P., Hau, Peter, Salzberger, Bernd, Schnitzler, Paul, Poeck, Hendrik, Elinav, Eran, Merle, Uta, and Stein-Thoeringer, Christoph K.

Published
2022

35. Inhibition of aurora kinases for tailored risk-adapted treatment of multiple myeloma

Author

Hose, Dirk, Rème, Thierry, Meissner, Tobias, Moreaux, Jérôme, Seckinger, Anja, Lewis, Joe, Benes, Vladimir, Benner, Axel, Hundemer, Michael, Hielscher, Thomas, Shaughnessy, John D., Jr, Barlogie, Bart, Neben, Kai, Krämer, Alwin, Hillengass, Jens, Bertsch, Uta, Jauch, Anna, De Vos, John, Rossi, Jean-François, Möhler, Thomas, Blake, Jonathon, Zimmermann, Jürgen, Klein, Bernard, and Goldschmidt, Hartmut

Published
2009
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36. Impact of KMT2A-PTD Mutational Subgroups on Outcome of AML Patients after Induction Therapy and Allogeneic Hematopoietic Cell Transplantation

Author

Kunadt, Desiree, Zukunft, Sven, Metzeler, Klaus H, Röllig, Christoph, Schliemann, Christoph, Braess, Jan, Müller-Tidow, Carsten, Kraemer, Alwin, Scholl, Sebastian, Hilgendorf, Inken, Jost, Edgar, Steffen, Björn, Bug, Gesine, Einsele, Hermann, Schäfer-Eckart, Kerstin, Krause, Stefan W., Hänel, Mathias, Schroeder, Thomas, Kaufmann, Martin, Middeke, Jan Moritz, Sockel, Katja, Ruhnke, Leo, Platzbecker, Uwe, Serve, Hubert, Stelljes, Matthias, Baldus, Claudia D, Neubauer, Andreas, Schetelig, Johannes, Poitz, David, Thiede, Christian, Bornhäuser, Martin, and Stölzel, Friedrich

Published
2023
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38. Remission and Survival after Single Versus Double Induction with 7+3 for Newly Diagnosed Acute Myeloid Leukemia: Results from the Planned Interim Analysis of Randomized Controlled SAL-Daunodouble Trial

Author

Röllig, Christoph, Steffen, Björn, Alakel, Nael, Herbst, Regina, Noppeney, Richard, Hanoun, Maher, Racil, Zdenek, Schäfer-Eckart, Kerstin, Krämer, Alwin, Neubauer, Andreas, Baldus, Claudia D, Schliemann, Christoph, Kaufmann, Martin, Mertova, Jolana, Jost, Edgar, Niemann, Dirk, Novak, Jan, Krause, Stefan W, Scholl, Sebastian, Held, Gerhard, Parmentier, Stefani B., Szotkowski, Tomáš, Zak, Pavel, Rank, Andreas, Wass, Maxi, Buske, Sebastian, Kramer, Michael, Fiebig, Frank, Haake, Annett, Schetelig, Johannes, Platzbecker, Uwe, Thiede, Christian, Müller-Tidow, Carsten, Berdel, Wolfgang E., Serve, Hubert, Ehninger, Gerhard, Mayer, Jiri, and Bornhäuser, Martin

Published
2020
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40. Aneuploidy correlated 100% with chemical transformation of Chinese hamster cells

Author

Li, Ruhong, Yerganian, George, Duesberg, Peter, Kraemer, Alwin, Willer, Andreas, Rausch, Charlotte, and Hehlmann, Ruediger

Subjects
Aneuploidy -- Research, Cancer cells -- Research, Gene mutations -- Research, Hamsters -- Physiological aspects, Science and technology
Abstract

Aneuploidy or chromosome imbalance is the most massive genetic abnormality of cancer cells. It used to be considered the cause of cancer when it was discovered more than 100 years ago. Since the discovery of the gene, the aneuploidy hypothesis has lost ground to the hypothesis that mutation of cellular genes causes cancer. According to this hypothesis, cancers are diploid and aneuploidy is secondary or nonessential. Here we reexamine the aneuploidy hypothesis in view of the fact that nearly all solid cancers are aneuploid, that many carcinogens are nongenotoxic, and that mutated genes from cancer cells do not transform diploid human or animal cells. By regrouping the gene pool - as in speciation - aneuploidy inevitably will alter many genetic programs. This genetic revolution can explain the numerous unique properties of cancer cells, such as invasiveness, dedifferentiation, distinct morphology, and specific surface antigens, much better than gene mutation, which is limited by the conservation of the existing chromosome structure. To determine whether aneuploidy is a cause or a consequence of transformation, we have analyzed the chromosomes of Chinese hamster embryo (CHE) cells transformed in vitro. This system allows (i) detection of transformation within 2 months and thus about 5 months sooner than carcinogenesis and (ii) the generation of many more transformants per cost than carcinogenesis. To minimize mutation of cellular genes, we have used nongenotoxic carcinogens. It was found that 44 out of 44 colonies of CHE cells transformed by benz[a]pyrene, methylcholanthrene, dimethyl-benzanthracene, and colcemid, or spontaneously were between 50 and 100% aneuploid. Thus, aneuploidy originated with transformation. Two of two chemically transformed colonies tested were tumorigenic 2 months after inoculation into hamsters. The cells of transformed colonies were heterogeneous in chromosome number, consistent with the hypothesis that aneuploidy can perpetually destabilize the chromosome number because it unbalances the elements of the mitotic apparatus. Considering that all 44 transformed colonies analyzed were aneuploid, and the early association between aneuploidy, transformation, and tumorigenicity, we conclude that aneuploidy is the cause rather than a consequence of transformation.

Published
1997

43. RAS activation and CDKN2A deletion to predict prognosis in cancer of unknown primary.

Author

Bochtler, Tilmann, primary, Reiling, Anna, additional, Endris, Volker, additional, Hielscher, Thomas, additional, Volckmar, Anna-Lena, additional, Neumann, Olaf, additional, Kirchner, Martina, additional, Budczies, Jan, additional, Heukamp, Lukas, additional, Leichsenring, Jonas, additional, Allgäuer, Michael, additional, Schirmacher, Peter, additional, Stenzinger, Albrecht, additional, and Kraemer, Alwin, additional

Published
2019
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44. Integrated Histogenetic Analysis Reveals BAP1-Mutated Epithelioid Mesothelioma in a Patient With Cancer of Unknown Primary

Author

Bochtler, Tilmann, Endris, Volker, Reiling, Anna, Leichsenring, Jonas, Schweiger, Michal R., Klein, Sebastian, Stoegbauer, Fabian, Goeppert, Benjamin, Schirmacher, Peter, Kraemer, Alwin, Stenzinger, Albrecht, Bochtler, Tilmann, Endris, Volker, Reiling, Anna, Leichsenring, Jonas, Schweiger, Michal R., Klein, Sebastian, Stoegbauer, Fabian, Goeppert, Benjamin, Schirmacher, Peter, Kraemer, Alwin, and Stenzinger, Albrecht

Abstract

This case report presents a male patient with epithelioid mesothelioma that was initially misdiagnosed as cancer of unknown primary (CUP) and correctly identified using molecular panel sequencing. The patient had a prior history of colon and breast cancer. To assess the enlarged mediastinal lymph nodes, retrosternal lymphadenectomy was performed in 2016. The lymph nodes were histologically deemed unrelated to the known breast cancer by the reference pathologist, thus leading to the diagnosis of a CUP syndrome. When the patient presented to our center, targeted deep sequencing of both breast cancer and presumed CUP was performed to address the clonal relationship between both malignancies. A missense mutation in BAP1 was revealed in both samples, with coverage data indicating a germline event. The patient was subsequently counseled by a human geneticist and underwent genetic testing, which confirmed the germline nature of this mutation. Collectively, these data led to the diagnosis of BAP1 (BRCA1-associated protein-1) tumor predisposition syndrome (TPDS). With the knowledge of an underlying BAP1 mutation and its known frequent association with epithelioid mesothelioma, the histology was reassessed and the diagnosis was revised to epithelioid mesothelioma. At this point, peritoneal involvement of mesothelioma could be diagnosed and histologically confirmed. This case illustrates the potential of integrated histopathologic and molecular diagnostics in helping to decipher CUP syndromes and establish the correct diagnosis. Additionally, this case highlights typical features of BAP1 TPDS with its general susceptibility to cancers, with pleural and peritoneal mesotheliomas as most prevalent clinical entities and the typically more benign course of these epithelioid mesotheliomas compared with BAP1-unrelated cases of mesotheliomas.

Published
2018

47. Impact of Genetic Abnormalities and Measurable Residual Disease Levels on Outcome in Patients with MDS/AML Pre-Emptively Treated with Azacitidine: Correlative Results of the Prospective RELAZA2 Trial

Author

Kayser, Sabine, Middeke, Jan Moritz, Kramer, Michael, Sockel, Katja, Stasik, Sebastian, Herbst, Regina, Fransecky, Lars R., Wolf, Dominik, Martin, Schumacher, Krämer, Alwin, Noppeney, Richard, Novotny, Juergen, Bug, Gesine, Götze, Katharina S., Spiekermann, Karsten, Stelljes, Matthias, Mikesch, Jan-Henrik, Subklewe, Marion, Schubert, Antje, Mütherig, Anke, Bochtler, Tilmann, Mende, Marika, Stoelzel, Friedrich, Kubasch, Anne, Von Bonin, Malte, Haenel, Mathias, Duehrsen, Ulrich, Schetelig, Johannes, Rollig, Christoph, Baldus, Claudia D, Ehninger, Gerhard, Müller-Tidow, Carsten, Serve, Hubert, Bornhäuser, Martin, Platzbecker, Uwe, and Thiede, Christian

Published
2020
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48. Clinical Outcomes and Characteristics of Patients (pts) with FLT3–Internal Tandem Duplication (FLT3-ITD)–Mutated Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML) Undergoing Hematopoietic Stem Cell Transplant (HSCT) after Quizartinib (Q) or Salvage Chemotherapy (SC) in the Quantum-R Trial

Author

Ganguly, Siddhartha, Cortes, Jorge E., Krämer, Alwin, Levis, Mark J., Martinelli, Giovanni, Perl, Alexander E., Russell, Nigel H., Arunachalam, Meena, Gammon, Guy, Lesegretain, Arnaud, Mires, Derek E., and Khaled, Samer K.

Published
2020
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49. Pan-Mutant-IDH1 Inhibitor Bay-1436032 Is Highly Effective Against Human IDH1 Mutant Acute Myeloid Leukemia In Vivo

Author

Heuser, Michael, primary, Herbst, Lena, additional, Pusch, Stefan, additional, Klett, Lara, additional, Goparaju, Ramya, additional, Stichel, Damian, additional, Kaulfuss, Stefan, additional, Panknin, Olaf, additional, Zimmermann, Katja, additional, Toschi, Luisella, additional, Neuhaus, Roland, additional, Haegebarth, Andrea, additional, Rehwinkel, Hartmut, additional, Hess-Stumpp, Holger, additional, Bauser, Markus, additional, Bochtler, Tilmann, additional, Struys, Eduard A, additional, Sharma, Amit, additional, Abdellatif, Abdellatif, additional, Geffers, Robert, additional, Araujo Cruz, Michelle M, additional, Thol, Felicitas, additional, Gabdoulline, Razif, additional, Ganser, Arnold, additional, Ho, Anthony D, additional, von Deimling, Andreas, additional, Rippe, Karsten, additional, Chaturvedi, Anuhar, additional, and Kraemer, Alwin, additional

Published
2016
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50. Differences Between CEBPA bZIP and TAD Mutations and Their Effect on Outcome-an Analysis in 4578 Patients with Acute Myeloid Leukemia

Author

Georgi, Julia-Annabell, primary, Taube, Franziska, additional, Kramer, Michael, additional, Herold, Sylvia, additional, Schaefer-Eckart, Kerstin, additional, Schmitz, Norbert, additional, Eberlein, Christian, additional, Stasik, Sebastian, additional, Aulitzky, Walter E, additional, Kraemer, Alwin, additional, Roesler, Wolf, additional, Haenel, Mathias, additional, Einsele, Hermann, additional, Baldus, Claudia D., additional, Middeke, Jan Moritz, additional, Platzbecker, Uwe, additional, Roellig, Christoph, additional, Serve, Hubert, additional, Berdel, Wolfgang E, additional, Ehninger, Gerhard, additional, Bornhaeuser, Martin, additional, Schetelig, Johannes, additional, and Thiede, Christian, additional

Published
2016
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