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2. Treatment with the apoptosis inhibitor Asunercept reduces clone sizes in patients with lower risk Myelodysplastic Neoplasms

Author

Streuer, Alexander, Jann, Johann-Christoph, Boch, Tobias, Mossner, Maximilian, Riabov, Vladimir, Schmitt, Nanni, Altrock, Eva, Xu, Qingyu, Demmerle, Marie, Nowak, Verena, Oblaender, Julia, Palme, Iris, Weimer, Nadine, Rapp, Felicitas, Metzgeroth, Georgia, Hecht, Anna, Höger, Thomas, Merz, Christian, Hofmann, Wolf-Karsten, Nolte, Florian, and Nowak, Daniel

Published
2024
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3. Breaking the Architecture Barrier: A Method for Efficient Knowledge Transfer Across Networks

Author

Czyzewski, Maciej A., Nowak, Daniel, and Piechowiak, Kamil

Subjects
Computer Science - Machine Learning
Abstract

Transfer learning is a popular technique for improving the performance of neural networks. However, existing methods are limited to transferring parameters between networks with same architectures. We present a method for transferring parameters between neural networks with different architectures. Our method, called DPIAT, uses dynamic programming to match blocks and layers between architectures and transfer parameters efficiently. Compared to existing parameter prediction and random initialization methods, it significantly improves training efficiency and validation accuracy. In experiments on ImageNet, our method improved validation accuracy by an average of 1.6 times after 50 epochs of training. DPIAT allows both researchers and neural architecture search systems to modify trained networks and reuse knowledge, avoiding the need for retraining from scratch. We also introduce a network architecture similarity measure, enabling users to choose the best source network without any training., Comment: 23 pages, 16 figures

Published
2022

4. Abstract: Multistage Registration of CT and Biopsy CT Images of Lung Tumors

Author

Strittmatter, Anika, primary, Hertel, Alexander, additional, Diehl, Steffen, additional, Froelich, Matthias F., additional, Schoenberg, Stefan O., additional, Loges, Sonja, additional, Boch, Tobias, additional, Nowak, Daniel, additional, Streuer, Alexander, additional, Schad, Lothar R., additional, and Zöllner, Frank G., additional

Published
2024
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5. Instructive interaction between myelodysplastic hematopoiesis and the bone marrow microenvironment at the single-cell level

Author

Jann, Johann-Christoph, Schmitt, Nanni, Streuer, Alexander, Xu, Qingyu, Riabov, Vladimir, Altrock, Eva, Weimer, Nadine, Nowak, Verena, Obländer, Julia, Palme, Iris, Göl, Melda, Demmerle, Marie, Rapp, Felicitas, Siegel, Fabian, Steiner, Laurenz, Ghazal, Mahmoud, Duda, Angelika, Haselmann, Verena, Darwich, Ali, Jawhar, Ahmed, Jawhar, Mohamad, Metzgeroth, Georgia, Hofmann, Wolf-Karsten, and Nowak, Daniel

Published
2024
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6. Functional analysis of structural variants in single cells using Strand-seq

Author

Jeong, Hyobin, Grimes, Karen, Rauwolf, Kerstin K., Bruch, Peter-Martin, Rausch, Tobias, Hasenfeld, Patrick, Benito, Eva, Roider, Tobias, Sabarinathan, Radhakrishnan, Porubsky, David, Herbst, Sophie A., Erarslan-Uysal, Büşra, Jann, Johann-Christoph, Marschall, Tobias, Nowak, Daniel, Bourquin, Jean-Pierre, Kulozik, Andreas E., Dietrich, Sascha, Bornhauser, Beat, Sanders, Ashley D., and Korbel, Jan O.

Published
2023
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7. Distinct and targetable role of calcium-sensing receptor in leukaemia

Author

Pereira, Raquel S., Kumar, Rahul, Cais, Alessia, Paulini, Lara, Kahler, Alisa, Bravo, Jimena, Minciacchi, Valentina R., Krack, Theresa, Kowarz, Eric, Zanetti, Costanza, Godavarthy, Parimala Sonika, Hoeller, Fabian, Llavona, Pablo, Stark, Tabea, Tascher, Georg, Nowak, Daniel, Meduri, Eshwar, Huntly, Brian J. P., Münch, Christian, Pampaloni, Francesco, Marschalek, Rolf, and Krause, Daniela S.

Published
2023
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8. Inhibition of lysyl oxidases synergizes with 5-azacytidine to restore erythropoiesis in myelodysplastic and myeloid malignancies

Author

Xu, Qingyu, Streuer, Alexander, Jann, Johann-Christoph, Altrock, Eva, Schmitt, Nanni, Flach, Johanna, Sens-Albert, Carla, Rapp, Felicitas, Wolf, Julia, Nowak, Verena, Weimer, Nadine, Obländer, Julia, Palme, Iris, Kuzina, Mariia, Jawhar, Ahmed, Darwich, Ali, Weis, Cleo-Aron, Marx, Alexander, Wuchter, Patrick, Costina, Victor, Jäger, Evelyn, Sperk, Elena, Neumaier, Michael, Fabarius, Alice, Metzgeroth, Georgia, Nolte, Florian, Steiner, Laurenz, Levkin, Pavel A., Jawhar, Mohamad, Hofmann, Wolf-Karsten, Riabov, Vladimir, and Nowak, Daniel

Published
2023
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9. Abstract: Multistage Registration of CT and Biopsy CT Images of Lung Tumors

Author

Strittmatter, Anika, Hertel, Alexander, Diehl, Steffen, Froelich, Matthias F., Schoenberg, Stefan O., Loges, Sonja, Boch, Tobias, Nowak, Daniel, Streuer, Alexander, Schad, Lothar R., Zöllner, Frank G., Gesellschaft für Informatik e.V. (GI), Maier, Andreas, editor, Deserno, Thomas M., editor, Handels, Heinz, editor, Maier-Hein, Klaus, editor, Palm, Christoph, editor, and Tolxdorff, Thomas, editor

Published
2024
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11. Antigen presentation safeguards the integrity of the hematopoietic stem cell pool

Author

Hernández-Malmierca, Pablo, Vonficht, Dominik, Schnell, Alexandra, Uckelmann, Hannah J., Bollhagen, Alina, Mahmoud, Mohamed A.A., Landua, Sophie-Luise, van der Salm, Elise, Trautmann, Christine L., Raffel, Simon, Grünschläger, Florian, Lutz, Raphael, Ghosh, Michael, Renders, Simon, Correia, Nádia, Donato, Elisa, Dixon, Karin O., Hirche, Christoph, Andresen, Carolin, Robens, Claudia, Werner, Paula S., Boch, Tobias, Eisel, David, Osen, Wolfram, Pilz, Franziska, Przybylla, Adriana, Klein, Corinna, Buchholz, Frank, Milsom, Michael D., Essers, Marieke A.G., Eichmüller, Stefan B., Hofmann, Wolf-Karsten, Nowak, Daniel, Hübschmann, Daniel, Hundemer, Michael, Thiede, Christian, Bullinger, Lars, Müller-Tidow, Carsten, Armstrong, Scott A., Trumpp, Andreas, Kuchroo, Vijay K., and Haas, Simon

Published
2022
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12. Humanized three-dimensional scaffold xenotransplantation models for myelodysplastic syndromes

Author

Altrock, Eva, Sens-Albert, Carla, Jann, Johann-Christoph, Flach, Johanna, Riabov, Vladimir, Schmitt, Nanni, Xu, Qingyu, Mehralivand, Arwin, Hecht, Anna, Steiner, Laurenz, Streuer, Alexander, Nowak, Verena, Obländer, Julia, Weimer, Nadine, Palme, Iris, Jawhar, Ahmed, Weis, Cleo-Aron, Weyer, Vanessa, Nolte, Florian, Jawhar, Mohamad, Metzgeroth, Georgia, Marx, Alexander, Groden, Christoph, Hofmann, Wolf-Karsten, and Nowak, Daniel

Published
2022
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13. Preclinical evaluation of eltrombopag in a PDX model of myelodysplastic syndromes

Author

Schmitt, Nanni, Jann, Johann-Christoph, Altrock, Eva, Flach, Johanna, Danner, Justine, Uhlig, Stefanie, Streuer, Alexander, Knaflic, Antje, Riabov, Vladimir, Xu, Qingyu, Mehralivand, Arwin, Palme, Iris, Nowak, Verena, Obländer, Julia, Weimer, Nadine, Haselmann, Verena, Jawhar, Ahmed, Darwich, Ali, Weis, Cleo-Aron, Marx, Alexander, Steiner, Laurenz, Jawhar, Mohamad, Metzgeroth, Georgia, Boch, Tobias, Nolte, Florian, Hofmann, Wolf-Karsten, and Nowak, Daniel

Published
2022
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14. Author Correction: Genome-wide association study identifies susceptibility loci for acute myeloid leukemia

Author

Lin, Wei-Yu, Fordham, Sarah E., Hungate, Eric, Sunter, Nicola J., Elstob, Claire, Xu, Yaobo, Park, Catherine, Quante, Anne, Strauch, Konstantin, Gieger, Christian, Skol, Andrew, Rahman, Thahira, Sucheston-Campbell, Lara, Wang, Junke, Hahn, Theresa, Clay-Gilmour, Alyssa I., Jones, Gail L., Marr, Helen J., Jackson, Graham H., Menne, Tobias, Collin, Mathew, Ivey, Adam, Hills, Robert K., Burnett, Alan K., Russell, Nigel H., Fitzgibbon, Jude, Larson, Richard A., Le Beau, Michelle M., Stock, Wendy, Heidenreich, Olaf, Alharbi, Abrar, Allsup, David J., Houlston, Richard S., Norden, Jean, Dickinson, Anne M., Douglas, Elisabeth, Lendrem, Clare, Daly, Ann K., Palm, Louise, Piechocki, Kim, Jeffries, Sally, Bornhäuser, Martin, Röllig, Christoph, Altmann, Heidi, Ruhnke, Leo, Kunadt, Desiree, Wagenführ, Lisa, Cordell, Heather J., Darlay, Rebecca, Andersen, Mette K., Fontana, Maria C., Martinelli, Giovanni, Marconi, Giovanni, Sanz, Miguel A., Cervera, José, Gómez-Seguí, Inés, Cluzeau, Thomas, Moreilhon, Chimène, Raynaud, Sophie, Sill, Heinz, Voso, Maria Teresa, Lo-Coco, Francesco, Dombret, Hervé, Cheok, Meyling, Preudhomme, Claude, Gale, Rosemary E., Linch, David, Gaal-Wesinger, Julia, Masszi, Andras, Nowak, Daniel, Hofmann, Wolf-Karsten, Gilkes, Amanda, Porkka, Kimmo, Milosevic Feenstra, Jelena D., Kralovics, Robert, Grimwade, David, Meggendorfer, Manja, Haferlach, Torsten, Krizsán, Szilvia, Bödör, Csaba, Stölzel, Friedrich, Onel, Kenan, and Allan, James M.

Published
2022
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16. Instructive interaction between myelodysplastic hematopoiesis and the bone marrow microenvironment at single cell level

Author

Jann, Johann-Christoph, primary, Schmitt, Nanni, additional, Streuer, Alexander, additional, Xu, Qingyu, additional, Riabov, Vladimir, additional, Altrock, Eva, additional, Weimer, Nadine, additional, Nowak, Verena, additional, Obländer, Julia, additional, Palme, Iris, additional, Göl, Melda, additional, Demmerle, Marie, additional, Rapp, Felicitas, additional, Siegel, Fabian, additional, Steiner, Laurenz, additional, Ghazal, Mahmoud, additional, Duda, Angelika, additional, Haselmann, Verena, additional, Darwich, Ali, additional, Jawhar, Ahmed, additional, Jawhar, Mohammad, additional, Metzgeroth, Georgia, additional, Hofmann, Wolf-Karsten, additional, and Nowak, Daniel, additional

Published
2024
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20. Single-cell proteo-genomic reference maps of the hematopoietic system enable the purification and massive profiling of precisely defined cell states

Author

Triana, Sergio, Vonficht, Dominik, Jopp-Saile, Lea, Raffel, Simon, Lutz, Raphael, Leonce, Daniel, Antes, Magdalena, Hernández-Malmierca, Pablo, Ordoñez-Rueda, Diana, Ramasz, Beáta, Boch, Tobias, Jann, Johann-Christoph, Nowak, Daniel, Hofmann, Wolf-Karsten, Müller-Tidow, Carsten, Hübschmann, Daniel, Alexandrov, Theodore, Benes, Vladimir, Trumpp, Andreas, Paulsen, Malte, Velten, Lars, and Haas, Simon

Published
2021
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21. A tractable multi-leader multi-follower peak-load-pricing model with strategic interaction

Author

Grimm, Veronika, Nowak, Daniel, Schewe, Lars, Schmidt, Martin, Schwartz, Alexandra, Zöttl, Gregor, Grimm, Veronika, Nowak, Daniel, Schewe, Lars, Schmidt, Martin, Schwartz, Alexandra, and Zöttl, Gregor

Abstract

While single-level Nash equilibrium problems are quite well understood nowadays, less is known about multi-leader multi-follower games. However, these have important applications, e.g., in the analysis of electricity and gas markets, where often a limited number of firms interacts on various subsequent markets. In this paper, we consider a special class of two-level multi-leader multi-follower games that can be applied, e.g., to model strategic booking decisions in the European entry-exit gas market. For this nontrivial class of games, we develop a solution algorithm that is able to compute the complete set of Nash equilibria instead of just individual solutions or a bigger set of stationary points. Additionally, we prove that for this class of games, the solution set is finite and provide examples for instances without any Nash equilibria in pure strategies. We apply the algorithm to a case study in which we compute strategic booking and nomination decisions in a model of the European entry-exit gas market system. Finally, we use our algorithm to provide a publicly available test library for the considered class of multi-leader multi-follower games. This library contains problem instances with different economic and mathematical properties so that other researchers in the field can test and benchmark newly developed methods for this challenging class of problems.

Published
2024

26. Genome-wide DNA methylation analysis pre- and post-lenalidomide treatment in patients with myelodysplastic syndrome with isolated deletion (5q)

Author

Hecht, Anna, Meyer, Julia A., Jann, Johann-Christoph, Sockel, Katja, Giagounidis, Aristoteles, Götze, Katharina S., Letsch, Anne, Haase, Detlef, Schlenk, Richard F., Haferlach, Torsten, Schafhausen, Philippe, Bug, Gesine, Lübbert, Michael, Thol, Felicitas, Büsche, Guntram, Schuler, Esther, Nowak, Verena, Obländer, Julia, Fey, Stephanie, Müller, Nadine, Metzgeroth, Georgia, Hofmann, Wolf-Karsten, Germing, Ulrich, Nolte, Florian, Reinwald, Mark, and Nowak, Daniel

Published
2021
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28. Variegated clonality and rapid emergence of new molecular lesions in xenografts of acute lymphoblastic leukemia are associated with drug resistance

Author

Nowak, Daniel, Liem, Natalia LM, Mossner, Maximilian, Klaumünzer, Marion, Papa, Rachael A, Nowak, Verena, Jann, Johann C, Akagi, Tadayuki, Kawamata, Norihiko, Okamoto, Ryoko, Thoennissen, Nils H, Kato, Motohiro, Sanada, Masashi, Hofmann, Wolf-Karsten, Ogawa, Seishi, Marshall, Glenn M, Lock, Richard B, and Koeffler, H Phillip

Subjects
Childhood Leukemia, Hematology, Genetics, Rare Diseases, Cancer, Clinical Research, Biotechnology, Human Genome, Pediatric Research Initiative, Pediatric Cancer, Pediatric, Animals, Antineoplastic Agents, Biopsy, Clone Cells, Cytarabine, DNA, Neoplasm, Deoxycytidine Kinase, Dexamethasone, Disease Progression, Drug Resistance, Neoplasm, Female, Gene Dosage, Heterografts, Humans, Male, Methotrexate, Mice, Mice, Inbred NOD, Mice, SCID, Mutation, Neoplasm Proteins, Neoplasm Transplantation, Neoplastic Stem Cells, Peptide Synthases, Polymorphism, Single Nucleotide, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Radiation Chimera, Sequence Analysis, DNA, Vincristine, Cardiorespiratory Medicine and Haematology, Immunology
Abstract

The use of genome-wide copy-number analysis and massive parallel sequencing has revolutionized the understanding of the clonal architecture of pediatric acute lymphoblastic leukemia (ALL) by demonstrating that this disease is composed of highly variable clonal ancestries following the rules of Darwinian selection. The current study aimed to analyze the molecular composition of childhood ALL biopsies and patient-derived xenografts with particular emphasis on mechanisms associated with acquired chemoresistance. Genomic DNA from seven primary pediatric ALL patient samples, 29 serially passaged xenografts, and six in vivo selected chemoresistant xenografts were analyzed with 250K single-nucleotide polymorphism arrays. Copy-number analysis of non-drug-selected xenografts confirmed a highly variable molecular pattern of variegated subclones. Whereas primary patient samples from initial diagnosis displayed a mean of 5.7 copy-number alterations per sample, serially passaged xenografts contained a mean of 8.2 and chemoresistant xenografts a mean of 10.5 copy-number alterations per sample, respectively. Resistance to cytarabine was explained by a new homozygous deletion of the DCK gene, whereas methotrexate resistance was associated with monoallelic deletion of FPGS and mutation of the remaining allele. This study demonstrates that selecting for chemoresistance in xenografted human ALL cells can reveal novel mechanisms associated with drug resistance.

Published
2015

29. Myelodysplastische Syndrome

Author

La Meir, Franziska, Boch, Tobias, Nowak, Daniel, Metzgeroth, Georgia, Hofmann, Wolf-Karsten, Wedding, Ulrich, Section editor, Ebert, Matthias, editor, Härtel, Nicolai, editor, and Wedding, Ulrich, editor

Published
2018
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30. Genome-wide association study identifies susceptibility loci for acute myeloid leukemia

Author

Lin, Wei-Yu, Fordham, Sarah E., Hungate, Eric, Sunter, Nicola J., Elstob, Claire, Xu, Yaobo, Park, Catherine, Quante, Anne, Strauch, Konstantin, Gieger, Christian, Skol, Andrew, Rahman, Thahira, Sucheston-Campbell, Lara, Wang, Junke, Hahn, Theresa, Clay-Gilmour, Alyssa I., Jones, Gail L., Marr, Helen J., Jackson, Graham H., Menne, Tobias, Collin, Mathew, Ivey, Adam, Hills, Robert K., Burnett, Alan K., Russell, Nigel H., Fitzgibbon, Jude, Larson, Richard A., Le Beau, Michelle M., Stock, Wendy, Heidenreich, Olaf, Alharbi, Abrar, Allsup, David J., Houlston, Richard S., Norden, Jean, Dickinson, Anne M., Douglas, Elisabeth, Lendrem, Clare, Daly, Ann K., Palm, Louise, Piechocki, Kim, Jeffries, Sally, Bornhäuser, Martin, Röllig, Christoph, Altmann, Heidi, Ruhnke, Leo, Kunadt, Desiree, Wagenführ, Lisa, Cordell, Heather J., Darlay, Rebecca, Andersen, Mette K., Fontana, Maria C., Martinelli, Giovanni, Marconi, Giovanni, Sanz, Miguel A., Cervera, José, Gómez-Seguí, Inés, Cluzeau, Thomas, Moreilhon, Chimène, Raynaud, Sophie, Sill, Heinz, Voso, Maria Teresa, Lo-Coco, Francesco, Dombret, Hervé, Cheok, Meyling, Preudhomme, Claude, Gale, Rosemary E., Linch, David, Gaal-Wesinger, Julia, Masszi, Andras, Nowak, Daniel, Hofmann, Wolf-Karsten, Gilkes, Amanda, Porkka, Kimmo, Milosevic Feenstra, Jelena D., Kralovics, Robert, Grimwade, David, Meggendorfer, Manja, Haferlach, Torsten, Krizsán, Szilvia, Bödör, Csaba, Stölzel, Friedrich, Onel, Kenan, and Allan, James M.

Published
2021
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32. Bone marrow sinusoidal endothelium controls terminal erythroid differentiation and reticulocyte maturation

Author

Heil, Joschka, Olsavszky, Victor, Busch, Katrin, Klapproth, Kay, de la Torre, Carolina, Sticht, Carsten, Sandorski, Kajetan, Hoffmann, Johannes, Schönhaber, Hiltrud, Zierow, Johanna, Winkler, Manuel, Schmid, Christian David, Staniczek, Theresa, Daniels, Deborah E., Frayne, Jan, Metzgeroth, Georgia, Nowak, Daniel, Schneider, Sven, Neumaier, Michael, Weyer, Vanessa, Groden, Christoph, Gröne, Hermann-Josef, Richter, Karsten, Mogler, Carolin, Taketo, Makoto Mark, Schledzewski, Kai, Géraud, Cyrill, Goerdt, Sergij, and Koch, Philipp-Sebastian

Published
2021
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34. Identification of leukemic and pre-leukemic stem cells by clonal tracking from single-cell transcriptomics

Author

Velten, Lars, Story, Benjamin A., Hernández-Malmierca, Pablo, Raffel, Simon, Leonce, Daniel R., Milbank, Jennifer, Paulsen, Malte, Demir, Aykut, Szu-Tu, Chelsea, Frömel, Robert, Lutz, Christoph, Nowak, Daniel, Jann, Johann-Christoph, Pabst, Caroline, Boch, Tobias, Hofmann, Wolf-Karsten, Müller-Tidow, Carsten, Trumpp, Andreas, Haas, Simon, and Steinmetz, Lars M.

Published
2021
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36. Genomic CDKN2A/2B deletions in adult Ph+ ALL are adverse despite allogeneic stem cell transplantation

Author

Pfeifer, Heike, Raum, Katharina, Markovic, Sandra, Nowak, Verena, Fey, Stephanie, Obländer, Julia, Pressler, Jovita, Böhm, Verena, Brüggemann, Monika, Wunderle, Lydia, Hüttmann, Andreas, Wäsch, Ralph, Beck, Joachim, Stelljes, Matthias, Viardot, Andreas, Lang, Fabian, Hoelzer, Dieter, Hofmann, Wolf-Karsten, Serve, Hubert, Weiss, Christel, Goekbuget, Nicola, Ottmann, Oliver G., and Nowak, Daniel

Published
2018
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37. Estradiol protection against toxic effects of catecholamine on electrical properties in human-induced pluripotent stem cell derived cardiomyocytes

Author

El-Battrawy, Ibrahim, Zhao, Zhihan, Lan, Huan, Schünemann, Jan-Dierk, Sattler, Katherine, Buljubasic, Fanis, Patocskai, Bence, Li, Xin, Yücel, Gökhan, Lang, Siegfried, Nowak, Daniel, Cyganek, Lukas, Bieback, Karen, Utikal, Jochen, Zimmermann, Wolfram-Hubertus, Ravens, Ursula, Wieland, Thomas, Borggrefe, Martin, Zhou, Xiao-Bo, and Akin, Ibrahim

Published
2018
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38. BACH2 mediates negative selection and p53-dependent tumor suppression at the pre-B cell receptor checkpoint

Author

Swaminathan, Srividya, Huang, Chuanxin, Geng, Huimin, Chen, Zhengshan, Harvey, Richard, Kang, Huining, Ng, Carina, Titz, Björn, Hurtz, Christian, Sadiyah, Mohammed Firas, Nowak, Daniel, Thoennissen, Gabriela B, Rand, Vikki, Graeber, Thomas G, Koeffler, H Phillip, Carroll, William L, Willman, Cheryl L, Hall, Andrew G, Igarashi, Kazuhiko, Melnick, Ari, and Müschen, Markus

Subjects
Biomedical and Clinical Sciences, Immunology, Cancer, Genetics, 1.1 Normal biological development and functioning, Underpinning research, Animals, Basic-Leucine Zipper Transcription Factors, Cell Death, Cell Differentiation, Cell Survival, Cell Transformation, Neoplastic, DNA-Binding Proteins, Gene Deletion, Gene Expression Regulation, Leukemic, Green Fluorescent Proteins, Immunoglobulin mu-Chains, Mice, Molecular Sequence Data, PAX5 Transcription Factor, Pre-B Cell Receptors, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Precursor Cells, B-Lymphoid, Proto-Oncogene Proteins c-bcl-6, Proto-Oncogene Proteins c-myc, RNA, Messenger, STAT5 Transcription Factor, Treatment Outcome, Tumor Suppressor Protein p53, V(D)J Recombination, Medical and Health Sciences, Biomedical and clinical sciences, Health sciences
Abstract

The B cell-specific transcription factor BACH2 is required for affinity maturation of B cells. Here we show that Bach2-mediated activation of p53 is required for stringent elimination of pre-B cells that failed to productively rearrange immunoglobulin VH-DJH gene segments. After productive VH-DJH gene rearrangement, pre-B cell receptor signaling ends BACH2-mediated negative selection through B cell lymphoma 6 (BCL6)-mediated repression of p53. In patients with pre-B acute lymphoblastic leukemia, the BACH2-mediated checkpoint control is compromised by deletions, rare somatic mutations and loss of its upstream activator, PAX5. Low levels of BACH2 expression in these patients represent a strong independent predictor of poor clinical outcome. In this study, we demonstrate that Bach2(+/+) pre-B cells resist leukemic transformation by Myc through Bach2-dependent upregulation of p53 and do not initiate fatal leukemia in transplant-recipient mice. Chromatin immunoprecipitation sequencing and gene expression analyses carried out by us revealed that BACH2 competes with BCL6 for promoter binding and reverses BCL6-mediated repression of p53 and other cell cycle checkpoint-control genes. These findings identify BACH2 as a crucial mediator of negative selection at the pre-B cell receptor checkpoint and a safeguard against leukemogenesis.

Published
2013

39. In vivo deficiency of both C/EBPβ and C/EBPε results in highly defective myeloid differentiation and lack of cytokine response.

Author

Akagi, Tadayuki, Thoennissen, Nils H, George, Ann, Crooks, Gay, Song, Jee Hoon, Okamoto, Ryoko, Nowak, Daniel, Gombart, Adrian F, and Koeffler, H Phillip

Subjects
Neutrophils, Macrophages, Animals, Animals, Newborn, Mice, Knockout, Mice, Bacterial Infections, Lipopolysaccharides, CCAAT-Enhancer-Binding Proteins, CCAAT-Enhancer-Binding Protein-beta, Receptors, Immunologic, Cytokines, Blotting, Western, Oligonucleotide Array Sequence Analysis, Cluster Analysis, Gene Expression Profiling, Reverse Transcriptase Polymerase Chain Reaction, Cell Differentiation, Protein Binding, Female, Male, Gene Regulatory Networks, Interferon-gamma, Promoter Regions, Genetic, Mice, 129 Strain, Newborn, Blotting, Western, Strain, Knockout, Promoter Regions, Genetic, Receptors, Immunologic, General Science & Technology
Abstract

The CCAAT/enhancer binding proteins (C/EBPs) are transcription factors involved in hematopoietic cell development and induction of several inflammatory mediators. Here, we generated C/EBPβ and C/EBPε double-knockout (bbee) mice and compared their phenotypes to those of single deficient (bbEE and BBee) and wild-type (BBEE) mice. The bbee mice were highly susceptible to fatal infections and died within 2-3 months. Morphologically, their neutrophils were blocked at the myelocytes/metamyelocytes stage, and clonogenic assays of bone marrow cells indicated a significant decrease in the number of myeloid colonies of the bbee mice. In addition, the proportion of hematopoietic progenitor cells [Lin(-)Sca1(+)c-Kit(+)] in the bone marrow of the bbee mice was significantly increased, reflecting the defective differentiation of the myeloid compartment. Furthermore, microarray expression analysis of LPS- and IFNγ-activated bone marrow-derived macrophages from bbee compared to single knockout mice revealed decreased expression of essential immune response-related genes and networks, including some direct C/EBP-targets such as Marco and Clec4e. Overall, the phenotype of the bbee mice is distinct from either the bbEE or BBee mice, demonstrating that both transcription factors are crucial for the maturation of neutrophils and macrophages, as well as the innate immune system, and can at least in part compensate for each other in the single knockout mice.

Published
2010

45. Significant improvement of bone marrow-derived MSC expansion from MDS patients by defined xeno-free medium

Author

Altrock, Eva, primary, Sens-Albert, Carla, additional, Hofmann, Franziska, additional, Riabov, Vladimir, additional, Schmitt, Nanni, additional, Xu, Qingyu, additional, Jann, Johann-Christoph, additional, Rapp, Felicitas, additional, Steiner, Laurenz, additional, Streuer, Alexander, additional, Nowak, Verena, additional, Obländer, Julia, additional, Weimer, Nadine, additional, Palme, Iris, additional, Göl, Melda, additional, Darwich, Ali, additional, Wuchter, Patrick, additional, Metzgeroth, Georgia, additional, Jawhar, Mohamad, additional, Hofmann, Wolf-Karsten, additional, and Nowak, Daniel, additional

Published
2023
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46. Functional analysis of structural variants in single cells using Strand-seq

Author

Jeong, Hyobin; https://orcid.org/0000-0002-1526-3343, Grimes, Karen; https://orcid.org/0000-0002-4805-2366, Rauwolf, Kerstin K, Bruch, Peter-Martin; https://orcid.org/0000-0002-9992-3109, Rausch, Tobias; https://orcid.org/0000-0001-5773-5620, Hasenfeld, Patrick; https://orcid.org/0000-0003-2319-2482, Benito, Eva, Roider, Tobias; https://orcid.org/0000-0002-6973-3531, Sabarinathan, Radhakrishnan, Porubsky, David; https://orcid.org/0000-0001-8414-8966, Herbst, Sophie A; https://orcid.org/0000-0001-8502-0366, Erarslan-Uysal, Büşra, Jann, Johann-Christoph; https://orcid.org/0000-0003-2200-0151, Marschall, Tobias; https://orcid.org/0000-0002-9376-1030, Nowak, Daniel; https://orcid.org/0000-0001-7130-7921, Bourquin, Jean-Pierre, Kulozik, Andreas E; https://orcid.org/0000-0003-1953-0848, Dietrich, Sascha, Bornhauser, Beat; https://orcid.org/0000-0003-2890-3191, Sanders, Ashley D; https://orcid.org/0000-0003-3945-0677, Korbel, Jan O; https://orcid.org/0000-0002-2798-3794, Jeong, Hyobin; https://orcid.org/0000-0002-1526-3343, Grimes, Karen; https://orcid.org/0000-0002-4805-2366, Rauwolf, Kerstin K, Bruch, Peter-Martin; https://orcid.org/0000-0002-9992-3109, Rausch, Tobias; https://orcid.org/0000-0001-5773-5620, Hasenfeld, Patrick; https://orcid.org/0000-0003-2319-2482, Benito, Eva, Roider, Tobias; https://orcid.org/0000-0002-6973-3531, Sabarinathan, Radhakrishnan, Porubsky, David; https://orcid.org/0000-0001-8414-8966, Herbst, Sophie A; https://orcid.org/0000-0001-8502-0366, Erarslan-Uysal, Büşra, Jann, Johann-Christoph; https://orcid.org/0000-0003-2200-0151, Marschall, Tobias; https://orcid.org/0000-0002-9376-1030, Nowak, Daniel; https://orcid.org/0000-0001-7130-7921, Bourquin, Jean-Pierre, Kulozik, Andreas E; https://orcid.org/0000-0003-1953-0848, Dietrich, Sascha, Bornhauser, Beat; https://orcid.org/0000-0003-2890-3191, Sanders, Ashley D; https://orcid.org/0000-0003-3945-0677, and Korbel, Jan O; https://orcid.org/0000-0002-2798-3794

Abstract

Somatic structural variants (SVs) are widespread in cancer, but their impact on disease evolution is understudied due to a lack of methods to directly characterize their functional consequences. We present a computational method, scNOVA, which uses Strand-seq to perform haplotype-aware integration of SV discovery and molecular phenotyping in single cells by using nucleosome occupancy to infer gene expression as a readout. Application to leukemias and cell lines identifies local effects of copy-balanced rearrangements on gene deregulation, and consequences of SVs on aberrant signaling pathways in subclones. We discovered distinct SV subclones with dysregulated Wnt signaling in a chronic lymphocytic leukemia patient. We further uncovered the consequences of subclonal chromothripsis in T cell acute lymphoblastic leukemia, which revealed c-Myb activation, enrichment of a primitive cell state and informed successful targeting of the subclone in cell culture, using a Notch inhibitor. By directly linking SVs to their functional effects, scNOVA enables systematic single-cell multiomic studies of structural variation in heterogeneous cell populations.

Published
2023

47. Mutational hierarchies in myelodysplastic syndromes dynamically adapt and evolve upon therapy response and failure

Author

Mossner, Maximilian, Jann, Johann-Christoph, Wittig, Janina, Nolte, Florian, Fey, Stephanie, Nowak, Verena, Obländer, Julia, Pressler, Jovita, Palme, Iris, Xanthopoulos, Christina, Boch, Tobias, Metzgeroth, Georgia, Röhl, Henning, Witt, Stephanie H., Dukal, Helene, Klein, Corinna, Schmitt, Steffen, Gelß, Patrick, Platzbecker, Uwe, Balaian, Ekaterina, Fabarius, Alice, Blum, Helmut, Schulze, Torsten J., Meggendorfer, Manja, Haferlach, Claudia, Trumpp, Andreas, Hofmann, Wolf-Karsten, Medyouf, Hind, and Nowak, Daniel

Published
2016
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48. Services, Retailing and Sales: A CONCEPTUAL FRAMEWORK AND EMPIRICAL INVESTIGATION OF SERVICE FAILURE-RECOVERY, RISK TRANSFER, AND INSTITUTIONAL TRUST.

Author

Nowak, Daniel

Subjects
SERVICE economy, ENTREPRENEURSHIP, CUSTOMER loyalty, CONSUMER behavior, CUSTOMER satisfaction
Abstract

The article focuses on how different service failure-recovery strategies affect institutional trust and customer risk perceptions. Topics include the impact of "buyer beware" practices versus "no-harm" service guarantees on institutional trust; the role of institutional entrepreneurship in aligning perceived and actual risk; the influence of service guarantees on customer behaviors and trust; and how adopting fair risk-sharing practices can enhance institutional trust and customer loyalty.

Published
2024

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