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51. Additional file 6 of Adverse stem cell clones within a single patient���s tumor predict clinical outcome in AML patients

Author

Zeller, Christina, Richter, Daniel, Jurinovic, Vindi, Valtierra-Guti��rrez, Ilse A., Jayavelu, Ashok Kumar, Mann, Matthias, Bagnoli, Johannes W., Hellmann, Ines, Herold, Tobias, Enard, Wolfgang, Vick, Binje, and Jeremias, Irmela

Abstract

Additional file 6. Figure S5. PDX clones display functional differences regarding growth behavior and treatment response in competitive in vivo experiments, related to Fig. 2B, C.

Published
2022
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52. X‐linked inhibitor of apoptosis protein represents a promising therapeutic target for relapsed/refractory ALL.

Author

Carlet, Michela, Schmelz, Karin, Vergalli, Jenny, Herold, Tobias, Senft, Daniela, Jurinovic, Vindi, Hoffmann, Thomas, Proba, Jutta, Weichert, Nina, Junghanß, Christian, Roth, Mareike, Eschenburg, Georg, Barz, Malwine, Henze, Günter, Eckert, Cornelia, Eggert, Angelika, Zuber, Johannes, Hundsdoerfer, Patrick, and Jeremias, Irmela

Abstract

Acute lymphoblastic leukemia (ALL) represents the most frequent malignancy in children, and relapse/refractory (r/r) disease is difficult to treat, both in children and adults. In search for novel treatment options against r/r ALL, we studied inhibitor of apoptosis proteins (IAP) and Smac mimetics (SM). SM‐sensitized r/r ALL cells towards conventional chemotherapy, even upon resistance against SM alone. The combination of SM and chemotherapy‐induced cell death via caspases and PARP, but independent from cIAP‐1/2, RIPK1, TNFα or NF‐κB. Instead, XIAP was identified to mediate SM effects. Molecular manipulation of XIAP in vivo using microRNA‐30 flanked shRNA expression in cell lines and patient‐derived xenograft (PDX) models of r/r ALL mimicked SM effects and intermediate XIAP knockdown‐sensitized r/r ALL cells towards chemotherapy‐induced apoptosis. Interestingly, upon strong XIAP knockdown, PDX r/r ALL cells were outcompeted in vivo, even in the absence of chemotherapy. Our results indicate a yet unknown essential function of XIAP in r/r ALL and reveal XIAP as a promising therapeutic target for r/r ALL. Synopsis: Smac mimetics sensitize relapsed/refractory acute leukemia (r/r ALL) cell lines towards chemotherapy, independently from TNFα, RIPK1, NFκB and cIAP1/2 signaling. Knockdown in PDX models shows that XIAP harbors an essential function in vivo and represents an important therapeutic target for r/r ALL. r/r ALL cell lines are sensitized to standard chemotherapy by co‐treatment with Smac mimetics (SM).TNFα, RIPK1, NFκB and cIAP1/2 are dispensable for apoptosis induced by the combination of SM and conventional chemotherapy in r/r ALL.To study the role of XIAP in vivo, a miR30‐based, fluorochrome‐guided system was established, with distinct promoters inducing different knockdown strengths.Moderate XIAP knockdown mimics the effects of SM and sensitizes r/r ALL to chemotherapy, making XIAP an interesting therapeutic target to enhance chemotherapy.In PDX models in vivo, strong XIAP knockdown alone reduces ALL growth, demonstrating that XIAP harbors an essential function and represents an interesting therapeutic target in r/r ALL. [ABSTRACT FROM AUTHOR]

Published
2023
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53. CHOP but Not Bendamustine Reverses EZH2 Y641 Mutation Induced MHC-I/II Loss in Human Lymphoma Models

Author

Adolph, Louisa Catharina, primary, Fichaux, Quentin, additional, Strobl, Carolin Dorothea, additional, Antoniolli, Martina, additional, Passerini, Verena, additional, Keay, William David, additional, Jurinovic, Vindi, additional, Lechner, Axel, additional, Hodson, Daniel J., additional, von Bergwelt, Michael, additional, Subklewe, Marion, additional, Rudelius, Martina, additional, and Weigert, Oliver, additional

Published
2021
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54. Multi-Dimensional Analysis of Adult Acute Myeloid Leukemia (AML) Landscape Cross-Continents Reveals Age Associated Trends in Mutations and Outcomes

Author

Cusan, Monica, primary, Larkin, Karilyn, additional, Nicolet, Deedra, additional, Jurinovic, Vindi, additional, Mrózek, Krzysztof, additional, Batcha, Aarif M. N., additional, Rothenberg-Thurley, Maja, additional, Schneider, Stephanie, additional, Sauerland, Maria Cristina, additional, Görlich, Dennis, additional, Krug, Utz, additional, Berdel, Wolfgang E., additional, Woermann, Bernhard Josef, additional, Hiddemann, Wolfgang, additional, Braess, Jan, additional, Spiekermann, Karsten, additional, Kohlschmidt, Jessica, additional, Blachly, James S., additional, Mims, Alice S., additional, Walker, Christopher J., additional, Oakes, Christopher C., additional, Orwick, Shelley, additional, Carroll, Andrew J, additional, Blum, William, additional, Powell, Bayard L., additional, Kolitz, Jonathan E, additional, Moore, Joseph O., additional, Mayer, Robert James, additional, Larson, Richard A., additional, Stone, Richard M., additional, Byrd, John C., additional, Metzeler, Klaus H., additional, Herold, Tobias, additional, and Eisfeld, Ann-Kathrin, additional

Published
2021
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55. An EZH2 Gene Expression Signature Is Predictive of Differential Efficacy of Chemotherapy Irrespective of EZH2 Mutation Status in Patients with Follicular Lymphoma Treated within the Gallium Trial

Author

Passerini, Verena, primary, Jurinovic, Vindi, additional, Bolen, Christopher R, additional, Knapp, Andrea, additional, Bottos, Alessia, additional, Richter, Julia, additional, Fitzgibbon, Jude, additional, Klapper, Wolfram, additional, Davies, Andrew, additional, Marcus, Robert, additional, von Bergwelt, Michael, additional, Nielsen, Tina, additional, Dreyling, Martin H., additional, Hiddemann, Wolfgang, additional, Unterhalt, Michael, additional, Hoster, Eva, additional, and Weigert, Oliver, additional

Published
2021
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56. Outcomes of men with HIV and germ cell cancer: Results from an international collaborative study

Author

Hentrich, Marcus Ulrich, primary, Bower, Mark, additional, Daugaard, Gedske, additional, Dieing, Annette, additional, Bickel, Markus, additional, Berretta, Massimiliano, additional, Lesmeister, Florian, additional, Jurinovic, Vindi, additional, Stoehr, Albrecht, additional, Heinzelbecker, Julia, additional, Krznaric, Ivanka, additional, Dieckmann, Klaus‐Peter, additional, Necchi, Andrea, additional, Maroto Rey, Pablo, additional, Rockstroh, Jürgen Kurt, additional, Brito, Margarida, additional, Pfister, David, additional, and Hoffmann, Christian, additional

Published
2021
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58. Risk Stratification of Patients with RUNX1-mutated Acute Myeloid Leukemia

Author

Rausch, Christian, Hornung, Roman, Batcha, Aarif M. N., Rothenberg-Thurley, Maja, Bamopoulos, Stefanos A., Jurinovic, Vindi, Ksienzyk, Bianka, Schneider, Stephanie, Dufour, Annika Maria, Neusser, Michaela, Sauerland, Maria Cristina, Görlich, Dennis, Krug, Utz, Berdel, Wolfgang E., Woermann, Bernhard J., Braess, Jan, Hiddemann, Wolfgang, Meggendorfer, Manja, Kern, Wolfgang, Haferlach, Torsten, Schetelig, Johannes, Middeke, Moritz, Stasik, Sebastian, Egger-Heidrich, Katharina, Röllig, Christoph, Bornhäuser, Martin, Thiede, Christian, Baldus, Claudia D, Müller-Tidow, Carsten, Platzbecker, Uwe, Serve, Hubert, Stock, Wendy, Uy, Geoffrey L, Byrd, John C., Nicolet, Deedra, Eisfeld, Ann-Kathrin, Mansmann, Ulrich, Spiekermann, Karsten, Metzeler, Klaus H, and Herold, Tobias

Published
2023
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59. Impact of Sex on Clinical Outcomes after CD19 CAR T-Cell Therapy for Large B-Cell Lymphoma: Response and Survival Are Significantly Superior in Female Compared to Male Patients

Author

Buecklein, Veit L., Rejeski, Kai, Perez, Ariel, Iacoboni, Gloria, Jurinovic, Vindi, Kharboutli, Soraya, Blumenberg, Viktoria, Ackermann, Josephine, Frölich, Lisa, Johnson, Grace, Patel, Kedar, Arciola, Brian, Mhaskar, Rahul, Schmidt, Christian, Wood, Anthony, Hoster, Eva, Mackensen, Andreas, Locke, Frederick L., von Bergwelt-Baildon, Michael, Mueller, Fabian, Barba, Pere, Jain, Michael D., and Subklewe, Marion

Published
2023
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60. D DX41-Low Expression Mimics Germline DDX41-Phenotype in Acute Myeloid Leukemia

Author

Shahbaz, Wajma, Jurinovic, Vindi, Batcha, Aarif M. N., Rausch, Christian, Rothenberg-Thurley, Maja, Dufour, Annika Maria, Ksienzyk, Bianka, Schneider, Stephanie, Neusser, Michaela, Sauerland, Maria Cristina, Görlich, Dennis, Berdel, Wolfgang E., Woermann, Bernhard J., Krug, Utz, Braess, Jan, Hiddemann, Wolfgang, Mansmann, Ulrich, Vosberg, Sebastian, Greif, Philipp A., Spiekermann, Karsten, Metzeler, Klaus H, and Herold, Tobias

Published
2023
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66. Evaluating upfront high-dose consolidation after R-CHOP for follicular lymphoma by clinical and genetic risk models

Author

Alig, Stefan, primary, Jurinovic, Vindi, additional, Shahrokh Esfahani, Mohammad, additional, Haebe, Sarah, additional, Passerini, Verena, additional, Hellmuth, Johannes C., additional, Gaitzsch, Erik, additional, Keay, William, additional, Tahiri, Natyra, additional, Zoellner, Anna, additional, Rosenwald, Andreas, additional, Klapper, Wolfram, additional, Stein, Harald, additional, Feller, Alfred, additional, Ott, German, additional, Staiger, Annette M., additional, Horn, Heike, additional, Hansmann, Martin L., additional, Pott, Christiane, additional, Unterhalt, Michael, additional, Schmidt, Christian, additional, Dreyling, Martin, additional, Alizadeh, Ash A., additional, Hiddemann, Wolfgang, additional, Hoster, Eva, additional, and Weigert, Oliver, additional

Published
2020
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69. Outcome of men with HIV-associated germ cell cancer: Results from an international collaborative study.

Author

Hentrich, Marcus, primary, Bower, Mark, additional, Daugaard, Gedske, additional, Dieing, Annette, additional, Bickel, Markus, additional, Berretta, Massimiliano, additional, Lesmeister, Florian, additional, Jurinovic, Vindi, additional, Stöhr, Albrecht, additional, Heinzelbecker, Julia, additional, Krznaric, Ivanka, additional, Dieckmann, Klaus-Peter, additional, Necchi, Andrea, additional, Maroto, José, additional, Rockstroh, Jürgen, additional, Goncalves, Margarida Brito, additional, Otremba, Burkhard Joerg, additional, and Hoffmann, Christian, additional

Published
2020
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70. Cathepsin S Alterations Induce a Tumor-Promoting Immune Microenvironment in Follicular Lymphoma

Author

Bararia, Deepak, primary, Hildebrand, Johannes A., additional, Stolz, Sebastian, additional, Haebe, Sarah, additional, Alig, Stefan, additional, Trevisani, Christopher P., additional, Osorio-Barrios, Francisco, additional, Bartoschek, Michael D., additional, Mentz, Michael, additional, Pastore, Alessandro, additional, Gaitzsch, Erik, additional, Heide, Michael, additional, Jurinovic, Vindi, additional, Rautter, Katharina, additional, Gunawardana, Jay, additional, Sabdia, Muhammed B., additional, Szczepanowski, Monika, additional, Richter, Julia, additional, Klapper, Wolfram, additional, Louissaint, Abner, additional, Ludwig, Christina, additional, Bultmann, Sebastian, additional, Leonhardt, Heinrich, additional, Eustermann, Sebastian, additional, Hopfner, Karl-Peter, additional, Hiddemann, Wolfgang, additional, von Bergwelt-Baildon, Michael, additional, Steidl, Christian, additional, Kridel, Robert, additional, Tobin, Joshua W.D., additional, Gandhi, Maher K., additional, Weinstock, David M., additional, Schmidt-Supprian, Marc, additional, Sárosi, Menyhárt B., additional, Rudelius, Martina, additional, Passerini, Verena, additional, Mautner, Josef, additional, and Weigert, Oliver, additional

Published
2020
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72. Localized- and advanced-stage follicular lymphomas differ in their gene expression profiles

Author

Staiger, Annette M., primary, Hoster, Eva, additional, Jurinovic, Vindi, additional, Winter, Stefan, additional, Leich, Ellen, additional, Kalla, Claudia, additional, Möller, Peter, additional, Bernd, Heinz-Wolfram, additional, Feller, Alfred C., additional, Koch, Karoline, additional, Klapper, Wolfram, additional, Stein, Harald, additional, Hansmann, Martin-Leo, additional, Hartmann, Sylvia, additional, Dreyling, Martin, additional, Weigert, Oliver, additional, Hiddemann, Wolfgang, additional, Herfarth, Klaus, additional, Rosenwald, Andreas, additional, Engelhard, Marianne, additional, Ott, German, additional, and Horn, Heike, additional

Published
2020
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73. Clinical presentation and differential splicing ofSRSF2, U2AF1andSF3B1mutations in patients with Acute Myeloid Leukaemia

Author

Bamopoulos, Stefanos A., primary, Batcha, Aarif M. N., additional, Jurinovic, Vindi, additional, Rothenberg-Thurley, Maja, additional, Janke, Hanna, additional, Ksienzyk, Bianka, additional, Philippou-Massier, Julia, additional, Graf, Alexander, additional, Krebs, Stefan, additional, Blum, Helmut, additional, Schneider, Stephanie, additional, Konstandin, Nikola, additional, Sauerland, Maria Cristina, additional, Görlich, Dennis, additional, Berdel, Wolfgang E., additional, Woermann, Bernhard J., additional, Bohlander, Stefan K., additional, Canzar, Stefan, additional, Mansmann, Ulrich, additional, Hiddemann, Wolfgang, additional, Braess, Jan, additional, Spiekermann, Karsten, additional, Metzeler, Klaus H., additional, and Herold, Tobias, additional

Published
2020
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74. Progression of Disease Within 24 Months in Follicular Lymphoma Is Associated With Reduced Intratumoral Immune Infiltration

Author

Tobin, Joshua W.D., primary, Keane, Colm, additional, Gunawardana, Jay, additional, Mollee, Peter, additional, Birch, Simone, additional, Hoang, Thanh, additional, Lee, Justina, additional, Li, Li, additional, Huang, Li, additional, Murigneux, Valentine, additional, Fink, J. Lynn, additional, Matigian, Nicholas, additional, Vari, Frank, additional, Francis, Santiyagu, additional, Kridel, Robert, additional, Weigert, Oliver, additional, Haebe, Sarah, additional, Jurinovic, Vindi, additional, Klapper, Wolfram, additional, Steidl, Christian, additional, Sehn, Laurie H., additional, Law, Soi-Cheng, additional, Wykes, Michelle N., additional, and Gandhi, Maher K., additional

Published
2019
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76. Evaluation of the m7-FLIPI in Patients with Follicular Lymphoma Treated within the Gallium Trial: EZH2 mutation Status May be a Predictive Marker for Differential Efficacy of Chemotherapy

Author

Jurinovic, Vindi, primary, Passerini, Verena, primary, Oestergaard, Mikkel Z, primary, Knapp, Andrea, primary, Mundt, Kirsten, primary, Araf, Shamzah, primary, Richter, Julia, primary, Fitzgibbon, Jude, primary, Klapper, Wolfram, primary, Marcus, Robert E., primary, Davies, Andrew, primary, Herold, Michael, primary, Hiddemann, Wolfgang, primary, Unterhalt, Michael, primary, Hoster, Eva, primary, and Weigert, Oliver, primary

Published
2019
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77. DNA Methylation Profiling of AML Reveals Epigenetic Subgroups with Distinct Clinical Outcome

Author

Vosberg, Sebastian, primary, Kerbs, Paul, additional, Jurinovic, Vindi, additional, Metzeler, Klaus H., additional, Amler, Susanne, additional, Sauerland, Cristina, additional, Görlich, Dennis, additional, Berdel, Wolfgang E., additional, Braess, Jan, additional, Hiddemann, Wolfgang, additional, Spiekermann, Karsten, additional, Herold, Tobias, additional, and Greif, Philipp A., additional

Published
2019
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78. Aberrant Cathepsin S Induces a Supportive Immune Microenvironment in Follicular Lymphoma

Author

Hildebrand, Johannes Adrian, primary, Bararia, Deepak, primary, Stolz, Sebastian, primary, Haebe, Sarah, primary, Alig, Stefan, primary, Bartoschek, Michael, primary, Boesl, Michael, primary, Pastore, Alessandro, primary, Gaitzsch, Erik, primary, Heide, Michael, primary, Jurinovic, Vindi, primary, Szczepanowski, Monika, primary, Klapper, Wolfram, primary, Louissaint, Abner, primary, Ludwig, Christina, primary, Bultmann, Sebastian, primary, Leonhardt, Heinrich, primary, Eustermann, Sebastian, primary, Hopfner, Karl-Peter, primary, Hiddemann, Wolfgang, primary, von Bergwelt, Michael, primary, Steidl, Christian, primary, Kridel, Robert, primary, Weinstock, David M, primary, Schmidt-Supprian, Marc, primary, Sárosi, Menyhárt B, primary, Passerini, Verena, primary, Mautner, Josef, primary, and Weigert, Oliver, primary

Published
2019
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79. Impact of age on clinical risk scores in follicular lymphoma

Author

Alig, Stefan, primary, Jurinovic, Vindi, additional, Pastore, Alessandro, additional, Haebe, Sarah, additional, Schmidt, Christian, additional, Zoellner, Anna-Katharina, additional, Dreyling, Martin, additional, Unterhalt, Michael, additional, Hoster, Eva, additional, Hiddemann, Wolfgang, additional, and Weigert, Oliver, additional

Published
2019
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80. Convergence of risk prediction models in follicular lymphoma

Author

Silva, Anjali, primary, Bassim, Sleiman, additional, Sarkozy, Clémentine, additional, Mottok, Anja, additional, Lackraj, Tracy, additional, Jurinovic, Vindi, additional, Brodtkorb, Marianne, additional, Lingjaerde, Ole Christian, additional, Sehn, Laurie H., additional, Gascoyne, Randy D., additional, Weigert, Oliver, additional, Steidl, Christian, additional, and Kridel, Robert, additional

Published
2019
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81. Large-scale benchmark study of survival prediction methods using multi-omics data.

Author

Herrmann, Moritz, Probst, Philipp, Hornung, Roman, Jurinovic, Vindi, and Boulesteix, Anne-Laure

Subjects
SURVIVAL rate, FORECASTING, RANDOM forest algorithms, PREDICTION models, MACHINE learning, KEY performance indicators (Management), SURVIVAL analysis (Biometry)
Abstract

Multi-omics data, that is, datasets containing different types of high-dimensional molecular variables, are increasingly often generated for the investigation of various diseases. Nevertheless, questions remain regarding the usefulness of multi-omics data for the prediction of disease outcomes such as survival time. It is also unclear which methods are most appropriate to derive such prediction models. We aim to give some answers to these questions through a large-scale benchmark study using real data. Different prediction methods from machine learning and statistics were applied on 18 multi-omics cancer datasets (35 to 1000 observations, up to 100 000 variables) from the database 'The Cancer Genome Atlas' (TCGA). The considered outcome was the (censored) survival time. Eleven methods based on boosting, penalized regression and random forest were compared, comprising both methods that do and that do not take the group structure of the omics variables into account. The Kaplan–Meier estimate and a Cox model using only clinical variables were used as reference methods. The methods were compared using several repetitions of 5-fold cross-validation. Uno's C-index and the integrated Brier score served as performance metrics. The results indicate that methods taking into account the multi-omics structure have a slightly better prediction performance. Taking this structure into account can protect the predictive information in low-dimensional groups—especially clinical variables—from not being exploited during prediction. Moreover, only the block forest method outperformed the Cox model on average, and only slightly. This indicates, as a by-product of our study, that in the considered TCGA studies the utility of multi-omics data for prediction purposes was limited. Contact:   moritz.herrmann@stat.uni-muenchen.de , +49 89 2180 3198 Supplementary information: Supplementary data are available at Briefings in Bioinformatics online. All analyses are reproducible using R code freely available on Github. [ABSTRACT FROM AUTHOR]

Published
2021
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82. Priority-Lasso: a simple hierarchical approach to the prediction of clinical outcome using multi-omics data

Author

Klau, Simon, Jurinovic, Vindi, Hornung, Roman, Herold, Tobias, and Boulesteix, Anne-Laure

Subjects
Cox Regression, Lasso, Multi-Omics Data, Penalized Regression, Prediction Model, priority-Lasso
Abstract

The inclusion of high-dimensional covariate data in prediction models has become a well-studied topic in the last decades. Although most of these methods do not account for possibly different types of variables in the set of covariates available in the same dataset, there are many such scenarios where the covariates can be structured in blocks of different types. To date, there exist a few computationally intensive approaches that make use of block structures of this kind. In this paper we present priority-Lasso, an intuitive and practical analysis strategy for building prediction models based on Lasso that takes such block structures into account. It requires the definition of a priority order of blocks of data. Lasso models are calculated successively for every block and the fitted values of every step are included as an offset in the fit of the next step. We apply priority-Lasso with different settings on a dataset of acute myeloid leukemia (AML) consisting of clinical variables, cytogenetics, gene mutations and expression variables, and compare its performance on an independent validation dataset to standard Lasso models. The results show that priority-Lasso is able to keep pace with Lasso in terms of prediction accuracy. Variables of blocks with higher priorities are favored over variables of blocks with lower priority, which results in an easily useable and transportable model for clinical practice.

Published
2017
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83. Chemotherapy-Free Combination of Obinutuzumab and Ibrutinib in First LINE Treatment of Follicular Lymphoma. the Alternative Study By the German Low Grade Lymphoma Study Group (GLSG)

Author

Schmidt, Christian, primary, Zoellner, Anna-Katharina, additional, Jurinovic, Vindi, additional, Sökler, Martin, additional, Forstpointner, Roswitha, additional, Haubner, Sascha, additional, Buske, Christian, additional, Viardot, Andreas, additional, Keller, Ulrich, additional, Pott, Christiane, additional, Graeven, Ullrich, additional, Marks, Reinhard, additional, Hänel, Mathias, additional, Liersch, Ruediger, additional, Dürig, Jan, additional, Hoster, Eva, additional, Unterhalt, Michael, additional, and Hiddemann, Wolfgang, additional

Published
2018
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84. Clinicogenetic Risk Models in Patients Randomized to Receive Consolidative Autologous Stem-Cell Transplantation after Frontline R-CHOP for Advanced Follicular Lymphoma: An Analysis from the GLSG2000 Trial

Author

Alig, Stefan, primary, Pastore, Alessandro, additional, Jurinovic, Vindi, additional, Häbe, Sarah, additional, Bararia, Deepak, additional, Passerini, Verena, additional, Keay, William, additional, Hellmuth, Johannes, additional, Rosenwald, Andreas, additional, Klapper, Wolfram, additional, Stein, Harald, additional, Feller, Alfred, additional, Ott, German, additional, Staiger, Annette M., additional, Horn, Heike, additional, Hansmann, Martin-Leo, additional, Pott, Christiane, additional, Forstpointner, Roswitha, additional, Hofmann, Wolf-Karsten, additional, Schmitz, Norbert, additional, Hess, Georg, additional, Unterhalt, Michael, additional, Dreyling, Martin H., additional, Zoellner, Anna-Katharina, additional, Schmidt, Christian, additional, Hoster, Eva, additional, Hiddemann, Wolfgang, additional, and Weigert, Oliver, additional

Published
2018
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87. Evolution of Cytogenetically Normal Acute Myeloid Leukemia During Therapy and Relapse: An Exome Sequencing Study of 50 Patients

Author

Greif, Philipp A., primary, Hartmann, Luise, additional, Vosberg, Sebastian, additional, Stief, Sophie M., additional, Mattes, Raphael, additional, Hellmann, Ines, additional, Metzeler, Klaus H., additional, Herold, Tobias, additional, Bamopoulos, Stefanos A., additional, Kerbs, Paul, additional, Jurinovic, Vindi, additional, Schumacher, Daniela, additional, Pastore, Friederike, additional, Bräundl, Kathrin, additional, Zellmeier, Evelyn, additional, Ksienzyk, Bianka, additional, Konstandin, Nikola P., additional, Schneider, Stephanie, additional, Graf, Alexander, additional, Krebs, Stefan, additional, Blum, Helmut, additional, Neumann, Martin, additional, Baldus, Claudia D., additional, Bohlander, Stefan K., additional, Wolf, Stephan, additional, Görlich, Dennis, additional, Berdel, Wolfgang E., additional, Wörmann, Bernhard J., additional, Hiddemann, Wolfgang, additional, and Spiekermann, Karsten, additional

Published
2018
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88. Impact of age on genetics and treatment efficacy in follicular lymphoma

Author

Alig, Stefan, primary, Jurinovic, Vindi, additional, Pastore, Alessandro, additional, Bararia, Deepak, additional, Häbe, Sarah, additional, Hellmuth, Johannes C., additional, Kridel, Robert, additional, Gascoyne, Randy, additional, Schmidt, Christian, additional, Zöllner, Anna-Katharina, additional, Buske, Christian, additional, Dreyling, Martin, additional, Unterhalt, Michael, additional, Hiddemann, Wolfgang, additional, Hoster, Eva, additional, and Weigert, Oliver, additional

Published
2018
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89. A 29-gene and cytogenetic score for the prediction of resistance to induction treatment in acute myeloid leukemia

Author

Herold, Tobias, primary, Jurinovic, Vindi, additional, Batcha, Aarif M. N., additional, Bamopoulos, Stefanos A., additional, Rothenberg-Thurley, Maja, additional, Ksienzyk, Bianka, additional, Hartmann, Luise, additional, Greif, Philipp A., additional, Phillippou-Massier, Julia, additional, Krebs, Stefan, additional, Blum, Helmut, additional, Amler, Susanne, additional, Schneider, Stephanie, additional, Konstandin, Nikola, additional, Sauerland, Maria Cristina, additional, Görlich, Dennis, additional, Berdel, Wolfgang E., additional, Wörmann, Bernhard J., additional, Tischer, Johanna, additional, Subklewe, Marion, additional, Bohlander, Stefan K., additional, Braess, Jan, additional, Hiddemann, Wolfgang, additional, Metzeler, Klaus H., additional, Mansmann, Ulrich, additional, and Spiekermann, Karsten, additional

Published
2017
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90. Adults with Philadelphia chromosome-like acute lymphoblastic leukemia frequently have IGH-CRLF2 and JAK2 mutations, persistence of minimal residual disease and poor prognosis

Author

Herold, Tobias, Schneider, Stephanie, Metzeler, Klaus Hans, Neumann, Martin, Hartmann, Luise, Roberts, Kathryn G., Konstandin, Nikola P., Greif, Philipp, Bräundl, Kathrin, Ksienzyk, Bianka, Huk, Natalia, Schneider, Irene, Zellmeier, Evelyn, Jurinovic, Vindi, Mansmann, Ulrich, Hiddemann, Wolfgang, Mullighan, Charles G., Bohlander, Stefan Klaus, Spiekermann, Karsten, Hoelzer, Dieter, Brüggemann, Monika, Baldus, Claudia, Dreyling, Martin, Gökbuget, Nicola, Herold, Tobias, Schneider, Stephanie, Metzeler, Klaus Hans, Neumann, Martin, Hartmann, Luise, Roberts, Kathryn G., Konstandin, Nikola P., Greif, Philipp, Bräundl, Kathrin, Ksienzyk, Bianka, Huk, Natalia, Schneider, Irene, Zellmeier, Evelyn, Jurinovic, Vindi, Mansmann, Ulrich, Hiddemann, Wolfgang, Mullighan, Charles G., Bohlander, Stefan Klaus, Spiekermann, Karsten, Hoelzer, Dieter, Brüggemann, Monika, Baldus, Claudia, Dreyling, Martin, and Gökbuget, Nicola

Abstract

Philadelphia-like B-cell precursor acute lymphoblastic leukemia (Ph-like ALL) is characterized by distinct genetic alterations and inferior prognosis in children and younger adults. The purpose of this study was a genetic and clinical characterization of Ph-like ALL in adults. Twenty-six (13%) of 207 adult patients (median age: 42 years) with B-cell precursor ALL (BCP-ALL) were classified as having Ph-like ALL using gene expression profiling. The frequency of Ph-like ALL was 27% among 95 BCP-ALL patients negative for BCR-ABL1 and KMT2A-rearrangements. IGH-CRLF2 rearrangements (6/16; P=0.002) and mutations in JAK2 (7/16; P<0.001) were found exclusively in the Ph-like ALL subgroup. Clinical and outcome analyses were restricted to patients treated in German Multicenter Study Group for Adult ALL (GMALL) trials 06/99 and 07/03 (n=107). The complete remission rate was 100% among both Ph-like ALL patients (n=19) and the “remaining BCP-ALL” cases (n=40), i.e. patients negative for BCR-ABL1 and KMT2A-rearrangements and the Ph-like subtype. Significantly fewer Ph-like ALL patients reached molecular complete remission (33% versus 79%; P=0.02) and had a lower probability of continuous complete remission (26% versus 60%; P=0.03) and overall survival (22% versus 64%; P=0.006) at 5 years compared to the remaining BCP-ALL patients. The profile of genetic lesions in adults with Ph-like ALL, including older adults, resembles that of pediatric Ph-like ALL and differs from the profile in the remaining BCP-ALL. Our study is the first to demonstrate that Ph-like ALL is associated with inferior outcomes in intensively treated older adult patients. Ph-like adult ALL should be recognized as a distinct, high-risk entity and further research on improved diagnostic and therapeutic approaches is needed.

Published
2017

91. Epithelial magnesium transport by TRPM6 is essential for prenatal development and adult survival

Author

Chubanov, Vladimir, primary, Ferioli, Silvia, additional, Wisnowsky, Annika, additional, Simmons, David G, additional, Leitzinger, Christin, additional, Einer, Claudia, additional, Jonas, Wenke, additional, Shymkiv, Yuriy, additional, Bartsch, Harald, additional, Braun, Attila, additional, Akdogan, Banu, additional, Mittermeier, Lorenz, additional, Sytik, Ludmila, additional, Torben, Friedrich, additional, Jurinovic, Vindi, additional, van der Vorst, Emiel PC, additional, Weber, Christian, additional, Yildirim, Önder A, additional, Sotlar, Karl, additional, Schürmann, Annette, additional, Zierler, Susanna, additional, Zischka, Hans, additional, Ryazanov, Alexey G, additional, and Gudermann, Thomas, additional

Published
2016
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92. Author response: Epithelial magnesium transport by TRPM6 is essential for prenatal development and adult survival

Author

Chubanov, Vladimir, primary, Ferioli, Silvia, additional, Wisnowsky, Annika, additional, Simmons, David G, additional, Leitzinger, Christin, additional, Einer, Claudia, additional, Jonas, Wenke, additional, Shymkiv, Yuriy, additional, Bartsch, Harald, additional, Braun, Attila, additional, Akdogan, Banu, additional, Mittermeier, Lorenz, additional, Sytik, Ludmila, additional, Torben, Friedrich, additional, Jurinovic, Vindi, additional, van der Vorst, Emiel PC, additional, Weber, Christian, additional, Yildirim, Önder A, additional, Sotlar, Karl, additional, Schürmann, Annette, additional, Zierler, Susanna, additional, Zischka, Hans, additional, Ryazanov, Alexey G, additional, and Gudermann, Thomas, additional

Published
2016
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93. Autologous Stem Cell Transplantation for Patients with Early Progression of Follicular Lymphoma- Retrospective Analysis of 2 Randomized Trials of the German Low Grade Lymphoma Study Group (GLSG)

Author

Jurinovic, Vindi, primary, Metzner, Bernd, additional, Pfreundschuh, Michael, additional, Schmitz, Norbert, additional, Wandt, Hannes, additional, Peschel, Christian, additional, Dreyling, Martin, additional, Hiddemann, Wolfgang, additional, Hoster, Eva, additional, Unterhalt, Michael, additional, and Weigert, Oliver, additional

Published
2016
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94. PS29MRC - a Novel Predictive Score for Response to Therapy in Acute Myeloid Leukemia

Author

Herold, Tobias, primary, Jurinovic, Vindi, primary, Metzeler, Klaus H., primary, Batcha, Aarif, primary, Bamopoulos, Stefan, primary, Rothenberg-Thurley, Maja, primary, Ksienzyk, Bianka, primary, Hartmann, Luise, primary, Greif, Philipp, primary, Phillippou-Massier, Julia, primary, Krebs, Stefan, primary, Blum, Helmut, primary, Amler, Susanne, primary, Schneider, Stephanie, primary, Sauerland, Christina, primary, Görlich, Dennis, primary, Büchner, Thomas, primary, Berdel, Wolfgang E, primary, Wörmann, Bernhard J, primary, Subklewe, Marion, primary, Fiegl, Michael, primary, Bohlander, Stefan K., primary, Braess, Jan, primary, Hiddemann, Wolfgang, primary, Mansmann, Ulrich, primary, and Spiekermann, Karsten, primary

Published
2016
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95. Clinical presentation and differential splicing of SRSF2, U2AF1and SF3B1mutations in patients with acute myeloid leukemia

Author

Bamopoulos, Stefanos A., Batcha, Aarif M. N., Jurinovic, Vindi, Rothenberg-Thurley, Maja, Janke, Hanna, Ksienzyk, Bianka, Philippou-Massier, Julia, Graf, Alexander, Krebs, Stefan, Blum, Helmut, Schneider, Stephanie, Konstandin, Nikola, Sauerland, Maria Cristina, Görlich, Dennis, Berdel, Wolfgang E., Woermann, Bernhard J., Bohlander, Stefan K., Canzar, Stefan, Mansmann, Ulrich, Hiddemann, Wolfgang, Braess, Jan, Spiekermann, Karsten, Metzeler, Klaus H., and Herold, Tobias

Abstract

Previous studies demonstrated that splicing factor mutations are recurrent events in hematopoietic malignancies with both clinical and functional implications. However, their aberrant splicing patterns in acute myeloid leukemia remain largely unexplored. In this study, we characterized mutations in SRSF2, U2AF1, and SF3B1, the most commonly mutated splicing factors. In our clinical analysis of 2678 patients, splicing factor mutations showed inferior relapse-free and overall survival, however, these mutations did not represent independent prognostic markers. RNA-sequencing of 246 and independent validation in 177 patients revealed an isoform expression profile which is highly characteristic for each individual mutation, with several isoforms showing a strong dysregulation. By establishing a custom differential splice junction usage pipeline, we accurately detected aberrant splicing in splicing factor mutated samples. A large proportion of differentially used junctions were novel, including several junctions in leukemia-associated genes. In SRSF2(P95H) mutants, we further explored the possibility of a cascading effect through the dysregulation of the splicing pathway. Furthermore, we observed a validated impact on overall survival for two junctions overused in SRSF2(P95H) mutants. We conclude that splicing factor mutations do not represent independent prognostic markers. However, they do have genome-wide consequences on gene splicing leading to dysregulated isoform expression of several genes.

Published
2020
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96. Acute myeloid leukemia with del(9q) is characterized by frequent mutations ofNPM1,DNMT3A, WT1and low expression ofTLE4

Author

Herold, Tobias, primary, Metzeler, Klaus H., additional, Vosberg, Sebastian, additional, Hartmann, Luise, additional, Jurinovic, Vindi, additional, Opatz, Sabrina, additional, Konstandin, Nikola P., additional, Schneider, Stephanie, additional, Zellmeier, Evelyn, additional, Ksienzyk, Bianka, additional, Graf, Alexander, additional, Krebs, Stefan, additional, Blum, Helmut, additional, Cristina Sauerland, Maria, additional, Büchner, Thomas, additional, Berdel, Wolfgang E., additional, Wörmann, Bernhard J., additional, Mansmann, Ulrich, additional, Hiddemann, Wolfgang, additional, Bohlander, Stefan K., additional, Spiekermann, Karsten, additional, and Greif, Philipp A., additional

Published
2016
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97. Adults with Philadelphia chromosome–like acute lymphoblastic leukemia frequently have IGH-CRLF2 and JAK2 mutations, persistence of minimal residual disease and poor prognosis

Author

Herold, Tobias, primary, Schneider, Stephanie, additional, Metzeler, Klaus H., additional, Neumann, Martin, additional, Hartmann, Luise, additional, Roberts, Kathryn G., additional, Konstandin, Nikola P., additional, Greif, Philipp A., additional, Bräundl, Kathrin, additional, Ksienzyk, Bianka, additional, Huk, Natalia, additional, Schneider, Irene, additional, Zellmeier, Evelyn, additional, Jurinovic, Vindi, additional, Mansmann, Ulrich, additional, Hiddemann, Wolfgang, additional, Mullighan, Charles G., additional, Bohlander, Stefan K., additional, Spiekermann, Karsten, additional, Hoelzer, Dieter, additional, Brüggemann, Monika, additional, Baldus, Claudia D., additional, Dreyling, Martin, additional, and Gökbuget, Nicola, additional

Published
2016
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98. A Clinicogenetic Risk Model (m7-FLIPI) Prospectively Identifies One-Half of Patients with Early Disease Progression of Follicular Lymphoma after First-Line Immunochemotherapy

Author

Martin Dreyling, Robert Kridel, Oliver Weigert, Wolfgang Hiddemann, Monika Szczepanowski, German Ott, Andreas Rosenwald, David M. Weinstock, Wolfram Klapper, Jonathan W. Friedberg, Randy D. Gascoyne, Michael Unterhalt, Andrew D. Zelenetz, Jurinovic Vindi, Annette M. Staiger, Joseph M. Connors, Laurie H. Sehn, Heike Horn, Stephen M. Ansell, and Eva Hoster

Subjects
medicine.medical_specialty, education.field_of_study, Intention-to-treat analysis, Performance status, business.industry, Surrogate endpoint, Immunology, Population, Follicular lymphoma, Cell Biology, Hematology, Odds ratio, medicine.disease, Biochemistry, Surgery, International Prognostic Index, Internal medicine, Cohort, medicine, education, business
Abstract

Background: Follicular lymphoma (FL) is the second most common nodal lymphoma worldwide and remains incurable for most patients (pts). FL is recognized to be a highly heterogeneous disease and a subset of pts experience remarkable poor outcome. In a recent study, 19-26% of pts receiving first-line R-CHOP experienced progression of disease (POD) within 24 months after diagnosis and had a 5-year (yr) overall survival (OS) of only 34-50%, as compared to a 5-yr OS of 90-94% for pts without POD within 24 months (Casulo et al., J Clin Oncol 2015). Consequently, event-free survival at 12 (EFS12) and 24 months (EFS24) have been suggested as novel surrogate endpoints for poor overall survival in clinical trials and useful for patient counseling (Maurer et al., ASH 2014). We have previously shown that a clinicogenetic risk model (m7-FLIPI) that includes the mutation status of seven genes (EZH2, ARID1A, MEF2B, EP300, FOXO1, CREBBP, and CARD11), the FL International Prognostic Index (FLIPI), and the Eastern Cooperative Oncology Group (ECOG) performance status, improves risk stratification for failure-free survival (FFS) and OS in pts with FL receiving first-line immunochemotherapy (Pastore et al., Lancet Oncology 2015). An online tool is available at: http://www.glsg.de/m7-flipi. It would be advantageous to determine prognosis prior to front-line therapy rather than after POD. Thus, we aimed to investigate the predictive utility of the m7-FLIPI for early POD. Patients and Methods: Clinical and mutation data were available from two independent cohorts: 151 pts who received R-CHOP and IFN maintenance as part of a randomized trial of the German Low-Grade Lymphoma Study Group (GLSG), and 107 pts from a population-based registry of the British Columbia Cancer Agency (BCCA) who received R-CVP. Among the latter, 93 (87%) received R-maintenance by intention to treat. All pts had symptomatic, advanced stage or bulky disease considered ineligible for curative radiotherapy, and a biopsy specimen obtained Results: In the GLSG cohort, median age was 57 yrs (range 27-77), 51% had high-risk FLIPI, and 5-yr failure-free survival (FFS) and OS rates were 66% and 83%, respectively (median follow-up for OS 7.7 yrs). In the BCCA cohort, median age was higher (62 yrs, 37-83), but high-risk FLIPI was similarly frequent (50%); 5-yr FFS and OS rates were 58% and 74%, respectively (median follow-up for OS 6.7 yrs). A total of 43 GLSG (28%) and 24 BCCA pts (22%) were classified as high-risk by m7-FLIPI, with a 5-yr OS of 65% and 42%, respectively. In the GLSG cohort, 8 (5%) and 29 pts (19%) had POD within 12 and 24 months, respectively, 4 and 10 pts were censored before POD12 and POD24 (table). High-risk m7-FLIPI pts were significantly more likely to experience early POD with an Odds Ratio (OR) of 20.80 (95% confidence interval (CI) 3.53-395.96; p=0.0052) for POD12 and 6.33 (95% CI 2.67-15.69; p In the GLSG and BCCA cohorts, the m7-FLIPI had a sensitivity of 88% and 50%, a specificity of 75% and 82%, a positive predictive value (PPV) of 16 and 33%, and a negative predictive value (NPV) of 96% and 90% to predict POD12. For POD24, sensitivity was 62% and 46%, specificity 79% and 86%, PPV 42% and 54%, and NPV 82% and 82%, respectively. Conclusion: We conclude that patients classified as high-risk m7-FLIPI are highly enriched among those with early progression of disease. However, approximately one-half of patients with progression by 24 months after therapy initiation are classified as low-risk m7-FLIPI. Thus, further efforts are needed to refine the m7-FLIPI and thereby capture additional cases that may benefit from innovative first-line approaches. Table. Population m7-FLIPI N POD12 POD24 GLSG Total 151 8/147* 29/141* High-risk 43 7 18 Low-risk 108 1 11 BCCA Total 107 16/107 28/107 High-risk 24 8 13 Low-risk 83 8 15 *Pts censored were removed Disclosures Ansell: Bristol-Myers Squibb: Research Funding; Celldex: Research Funding.

Published
2015

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