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2. Biallelic TET2 mutation sensitizes to 5’-azacitidine in acute myeloid leukemia

Author

Stölzel, Friedrich, Fordham, Sarah E, Nandana, Devi, Lin, Wei-Yu, Blair, Helen J, Elstob, Claire J, Bell, Hayden L, Mohr, Brigitte, Ruhnke, Leo, Kunadt, Desiree, Dill, Claudia, Allsop, Daniel A, Piddock, Rachel E, Soura, Emmanouela-Niki, Park, Catherine Vida, Fadly, Mohd, Rahman, Thahira, Alharbi, Abrar A, Wobus, Manja, Altmann, Heidi, Röllig, Christoph, Wagenführ, Lisa, Jones, Gail L, Menne, Tobias, Jackson, Graham H, Marr, Helen J, Fitzgibbon, Jude, Onel, Kenan, Meggendorfer, Manja, Robinson, Amber, Bziuk, Zuzanna, Bowes, Emily, Heidenreich, Olaf, Haferlach, Torsten, Villar, Sara, Ariceta, Beñat, Diaz, Rosa Ayala, Altschuler, Steven J, Wu, Lani, Prosper, Felipe, Montesinos, Pau, Martinez-Lopez, Joaquin, Bornhäuser, Martin, and Allan, James M

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Cancer, Hematology, Genetics, Pediatric, Pediatric Cancer, Rare Diseases, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Good Health and Well Being, Humans, Mice, Animals, Azacitidine, Leukemia, Myeloid, Acute, Kaplan-Meier Estimate, Mutation, DNA-Binding Proteins, Dioxygenases, Leukemias, Molecular genetics, Biomedical and clinical sciences, Health sciences
Abstract

Precision medicine can significantly improve outcomes for patients with cancer, but implementation requires comprehensive characterization of tumor cells to identify therapeutically exploitable vulnerabilities. Here, we describe somatic biallelic TET2 mutations in an elderly patient with acute myeloid leukemia (AML) that was chemoresistant to anthracycline and cytarabine but acutely sensitive to 5'-azacitidine (5'-Aza) hypomethylating monotherapy, resulting in long-term morphological remission. Given the role of TET2 as a regulator of genomic methylation, we hypothesized that mutant TET2 allele dosage affects response to 5'-Aza. Using an isogenic cell model system and an orthotopic mouse xenograft, we demonstrate that biallelic TET2 mutations confer sensitivity to 5'-Aza compared with cells with monoallelic mutations. Our data argue in favor of using hypomethylating agents for chemoresistant disease or as first-line therapy in patients with biallelic TET2-mutated AML and demonstrate the importance of considering mutant allele dosage in the implementation of precision medicine for patients with cancer.

Published
2023

3. Secondary-type mutations do not impact outcome in NPM1-mutated acute myeloid leukemia – implications for the European LeukemiaNet risk classification

Author

Eckardt, Jan-Niklas, Bill, Marius, Rausch, Christian, Metzeler, Klaus, Spiekermann, Karsten, Stasik, Sebastian, Sauer, Tim, Scholl, Sebastian, Hochhaus, Andreas, Crysandt, Martina, Brümmendorf, Tim H., Krug, Utz, Wörmann, Bernhard, Hiddemann, Wolfgang, Görlich, Dennis, Sauerland, Cristina, Steffen, Björn, Einsele, Hermann, Neubauer, Andreas, Burchert, Andreas, Schäfer-Eckart, Kerstin, Berdel, Wolfgang E., Schliemann, Christoph, Krause, Stefan W., Hänel, Mathias, Hanoun, Maher, Kaufmann, Martin, Fransecky, Lars, Braess, Jan, Ruhnke, Leo, Schetelig, Johannes, Middeke, Jan Moritz, Serve, Hubert, Baldus, Claudia D., Platzbecker, Uwe, Müller-Tidow, Carsten, Bornhäuser, Martin, Herold, Tobias, Thiede, Christian, and Röllig, Christoph

Published
2023
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4. Impact of BMI on patient outcome in acute myeloid leukaemia patients receiving intensive induction therapy: a real-world registry experience

Author

Enßle, Julius C., Wolf, Sebastian, Scheich, Sebastian, Weber, Sarah, Kramer, Michael, Ruhnke, Leo, Schliemann, Christoph, Mikesch, Jan-Henrik, Krause, Stefan, Sauer, Tim, Hanoun, Maher, Reinhardt, Hans Christian, Kraus, Sabrina, Kaufmann, Martin, Hänel, Mathias, Fransecky, Lars, Burchert, Andreas, Neubauer, Andreas, Crysandt, Martina, Jost, Edgar, Niemann, Dirk, Schäfer-Eckart, Kerstin, Held, Gerhard, Kaiser, Ulrich, Wass, Maxi, Schaich, Markus, Müller-Tidow, Carsten, Platzbecker, Uwe, Baldus, Claudia D., Bornhäuser, Martin, Röllig, Christoph, Serve, Hubert, and Steffen, Björn

Published
2023
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5. Intensified cytarabine dose during consolidation in adult AML patients under 65 years is not associated with survival benefit: real-world data from the German SAL-AML registry

Author

Hanoun, Maher, Ruhnke, Leo, Kramer, Michael, Hanoun, Christine, Schäfer-Eckart, Kerstin, Steffen, Björn, Sauer, Tim, Krause, Stefan W., Schliemann, Christoph, Mikesch, Jan-Henrik, Kaufmann, Martin, Hänel, Mathias, Jost, Edgar, Brümmendorf, Tim H., Fransecky, Lars, Kraus, Sabrina, Einsele, Hermann, Niemann, Dirk, Neubauer, Andreas, Kullmer, Johannes, Seggewiss-Bernhard, Ruth, Görner, Martin, Held, Gerhard, Kaiser, Ulrich, Scholl, Sebastian, Hochhaus, Andreas, Reinhardt, H. Christian, Platzbecker, Uwe, Baldus, Claudia D., Müller-Tidow, Carsten, Bornhäuser, Martin, Serve, Hubert, and Röllig, Christoph

Published
2023
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6. Validation of the revised 2022 European LeukemiaNet risk stratification in adult patients with acute myeloid leukemia

Author

Ruhnke, Leo, Bill, Marius, Zukunft, Sven, Eckardt, Jan-Niklas, Schäfer, Silvia, Stasik, Sebastian, Hanoun, Maher, Schroeder, Thomas, Fransecky, Lars, Steffen, Björn, Krause, Stefan W., Scholl, Sebastian, Hochhaus, Andreas, Sauer, Tim, Kraus, Sabrina, Schäfer-Eckart, Kerstin, Kaufmann, Martin, Jost, Edgar, Brümmendorf, Tim, Schliemann, Christoph, Mikesch, Jan-Henrik, Krug, Utz, Hänel, Mathias, Morgner, Anke, Schaich, Markus, Neubauer, Andreas, Repp, Roland, Niemann, Dirk, Seggewiss-Bernhardt, Ruth, Meinhardt, Achim, Kullmer, Johannes, Kaiser, Ulrich, Blau, Wolfgang, Kiani, Alexander, Grigoleit, Götz Ulrich, Giagounidis, Aristoteles, Wurm, Alexander A., Altmann, Heidi, Middeke, Jan Moritz, Schetelig, Johannes, Müller-Tidow, Carsten, Stölzel, Friedrich, Baldus, Claudia D., Platzbecker, Uwe, Serve, Hubert, Bornhäuser, Martin, Thiede, Christian, and Röllig, Christoph

Published
2024
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7. Germ line variant GFI1-36N affects DNA repair and sensitizes AML cells to DNA damage and repair therapy

Author

Frank, Daria, Patnana, Pradeep Kumar, Vorwerk, Jan, Mao, Lianghao, Gopal, Lavanya Mokada, Jung, Noelle, Hennig, Thorben, Ruhnke, Leo, Frenz, Joris Maximillian, Kuppusamy, Maithreyan, Autry, Robert, Wei, Lanying, Sun, Kaiyan, Mohammed Ahmed, Helal Mohammed, Künstner, Axel, Busch, Hauke, Müller, Heiko, Hutter, Stephan, Hoermann, Gregor, Liu, Longlong, Xie, Xiaoqing, Al-Matary, Yahya, Nimmagadda, Subbaiah Chary, Cano, Fiorella Charles, Heuser, Michael, Thol, Felicitas, Göhring, Gudrun, Steinemann, Doris, Thomale, Jürgen, Leitner, Theo, Fischer, Anja, Rad, Roland, Röllig, Christoph, Altmann, Heidi, Kunadt, Desiree, Berdel, Wolfgang E., Hüve, Jana, Neumann, Felix, Klingauf, Jürgen, Calderon, Virginie, Opalka, Bertram, Dührsen, Ulrich, Rosenbauer, Frank, Dugas, Martin, Varghese, Julian, Reinhardt, Hans Christian, von Bubnoff, Nikolas, Möröy, Tarik, Lenz, Georg, Batcha, Aarif M. N., Giorgi, Marianna, Selvam, Murugan, Wang, Eunice, McWeeney, Shannon K., Tyner, Jeffrey W., Stölzel, Friedrich, Mann, Matthias, Jayavelu, Ashok Kumar, and Khandanpour, Cyrus

Published
2023
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8. Using stroma-anchoring cytokines to augment ADCC: a phase 1 trial of F16IL2 and BI 836858 for posttransplant AML relapse

Author

Berdel, Andrew F., Ruhnke, Leo, Angenendt, Linus, Wermke, Martin, Röllig, Christoph, Mikesch, Jan-Henrik, Scheller, Annika, Hemmerle, Teresa, Matasci, Mattia, Wethmar, Klaus, Kessler, Torsten, Gerwing, Mirjam, Hescheler, Daniel, Schäfers, Michael, Hartmann, Wolfgang, Altvater, Bianca, Rossig, Claudia, Bornhäuser, Martin, Lenz, Georg, Stelljes, Matthias, Rueter, Bjoern, Neri, Dario, Berdel, Wolfgang E., and Schliemann, Christoph

Published
2022
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9. 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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11. Gemtuzumab ozogamicin plus midostaurin in combination with standard ‘7 + 3’ induction therapy in newly diagnosed AML: Results from the SAL‐MODULE phase I study

Author

Röllig, Christoph, primary, Schliemann, Christoph, additional, Ruhnke, Leo, additional, Fransecky, Lars, additional, Heydrich, Björn‐Niklas, additional, Hanoun, Maher, additional, Noppeney, Richard, additional, Schäfer‐Eckart, Kerstin, additional, Wendelin, Knut, additional, Mikesch, Jan‐Henrik, additional, Middeke, Jan Moritz, additional, Reimann, Manja, additional, Fiebig, Frank, additional, Zukunft, Sven, additional, Wermke, Martin, additional, Serve, Hubert, additional, Platzbecker, Uwe, additional, Müller‐Tidow, Carsten, additional, Baldus, Claudia D., additional, and Bornhäuser, Martin, additional

Published
2024
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12. 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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13. Germline variant GFI1-36N affects DNA repair and sensitizes AML cells to DNA damage and repair therapy

Author

Frank, Daria, primary, Patnana, Pradeep Kumar, additional, Vorwerk, Jan, additional, Mao, Lianghao, additional, Mokada Gopal, Lavanya, additional, Jung, Noelle, additional, Hennig, Thorben, additional, Ruhnke, Leo, additional, Frenz, Joris Maximillian, additional, Kuppusamy, Maithreyan, additional, Autry, Robert J, additional, Wei, Lanying, additional, Sun, Kaiyan, additional, Ahmed, Helal, additional, Künstner, Axel, additional, Busch, Hauke, additional, Müller, Heiko, additional, Hutter, Stephan, additional, Hoermann, Gregor, additional, Liu, Longlong, additional, Xie, Xiaoqing, additional, Al-Matary, Yahya, additional, Nimmagadda, Subbaiah Chary, additional, Charles Cano, Fiorella, additional, Heuser, Michael, additional, Thol, Felicitas R., additional, Göhring, Gudrun, additional, Steinemann, Doris, additional, Thomale, Jürgen, additional, Leitner, Theo, additional, Fischer, Anja, additional, Rad, Roland, additional, Röllig, Christoph, additional, Altmann, Heidi, additional, Kunadt, Desiree, additional, Berdel, Wolfgang E., additional, Hüve, Jana, additional, Neumann, Felix, additional, Klingauf, Jürgen, additional, Calderon, Virginie, additional, Opalka, Bertram, additional, Dührsen, Ulrich, additional, Rosenbauer, Frank, additional, Dugas, Martin, additional, Varghese, Julian, additional, Reinhardt, H. Christian H., additional, von Bubnoff, Nikolas, additional, Möröy, Tarik, additional, Lenz, Georg, additional, Batcha, Aarif M.N., additional, Giorgi, Marianna, additional, Selvam, Murugan, additional, Wang, Eunice S., additional, McWeeney, Shannon K., additional, Tyner, Jeffrey W., additional, Stölzel, Friedrich, additional, Mann, Matthias, additional, Jayavelu, Ashok Kumar, additional, and Khandanpour, Cyrus, additional

Published
2023
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14. P556: A NEW MULTIPLEX PCR TOOL ENABLES TIMELY IDENTIFICATION OF ACTIONABLE TARGETS FOR MOLECULAR-GUIDED THERAPY IN PATIENTS WITH ACUTE MYELOID LEUKEMIA

Author

Stölzel, Friedrich, primary, Ruhnke, Leo, additional, Altmann, Heidi, additional, Röllig, Christoph, additional, Bornhauser, Martin, additional, Chavakis, Triantafyllos, additional, Nestler, Stephanie, additional, Preussler, Matthias, additional, Weber, Anke, additional, and Poitz, David, additional

Published
2023
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15. S138: VALIDATION OF THE REVISED 2022 EUROPEAN LEUKEMIANET (ELN) RISK STRATIFICATION IN ADULT PATIENTS WITH ACUTE MYELOID LEUKEMIA

Author

Bill, Marius, primary, Ruhnke, Leo, additional, Zukunft, Sven, additional, Schäfer, Silvia, additional, Eckardt, Jan-Niklas, additional, Stasik, Sebastian, additional, Hanoun, Maher, additional, Schroeder, Thomas, additional, Fransecky, Lars, additional, Steffen, Björn, additional, Krause, Stefan W., additional, Scholl, Sebastian, additional, Hochhaus, Andreas, additional, Sauer, Tim, additional, Kraus, Sabrina, additional, Schäfer-Eckart, Kerstin, additional, Kaufmann, Martin, additional, Jost, Edgar, additional, Brümmendorf, Tim H, additional, Schliemann, Christoph, additional, Mikesch, Jan-Henrik, additional, Krug, Utz, additional, Hänel, Mathias, additional, Morgner, Anke, additional, Schaich, Markus, additional, Neubauer, Andreas, additional, Repp, Roland, additional, Niemann, Dirk, additional, Seggewiss-Bernhardt, Ruth, additional, Meinhardt, Achim, additional, Kullmer, Johannes, additional, Kaiser, Ulrich, additional, Blau, Wolfgang, additional, Kiani, Alexander, additional, Grigoleit, Götz Ulrich, additional, Giagounidis, Aristoteles, additional, Wurm, Alexander, additional, Altmann, Heidi, additional, Middeke, Jan Moritz, additional, Schetelig, Johannes, additional, Müller-Tidow, Carsten, additional, Stölzel, Friedrich, additional, Baldus, Claudia, additional, Platzbecker, Uwe, additional, Serve, Hubert, additional, Bornhäuser, Martin, additional, Thiede, Christian, additional, and Röllig, Christoph, additional

Published
2023
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16. Data from Comprehensive Genomic and Transcriptomic Analysis for Guiding Therapeutic Decisions in Patients with Rare Cancers

Author

Horak, Peter, primary, Heining, Christoph, primary, Kreutzfeldt, Simon, primary, Hutter, Barbara, primary, Mock, Andreas, primary, Hüllein, Jennifer, primary, Fröhlich, Martina, primary, Uhrig, Sebastian, primary, Jahn, Arne, primary, Rump, Andreas, primary, Gieldon, Laura, primary, Möhrmann, Lino, primary, Hanf, Dorothea, primary, Teleanu, Veronica, primary, Heilig, Christoph E., primary, Lipka, Daniel B., primary, Allgäuer, Michael, primary, Ruhnke, Leo, primary, Laßmann, Andreas, primary, Endris, Volker, primary, Neumann, Olaf, primary, Penzel, Roland, primary, Beck, Katja, primary, Richter, Daniela, primary, Winter, Ulrike, primary, Wolf, Stephan, primary, Pfütze, Katrin, primary, Geörg, Christina, primary, Meißburger, Bettina, primary, Buchhalter, Ivo, primary, Augustin, Marinela, primary, Aulitzky, Walter E., primary, Hohenberger, Peter, primary, Kroiss, Matthias, primary, Schirmacher, Peter, primary, Schlenk, Richard F., primary, Keilholz, Ulrich, primary, Klauschen, Frederick, primary, Folprecht, Gunnar, primary, Bauer, Sebastian, primary, Siveke, Jens Thomas, primary, Brandts, Christian H., primary, Kindler, Thomas, primary, Boerries, Melanie, primary, Illert, Anna L., primary, von Bubnoff, Nikolas, primary, Jost, Philipp J., primary, Spiekermann, Karsten, primary, Bitzer, Michael, primary, Schulze-Osthoff, Klaus, primary, von Kalle, Christof, primary, Klink, Barbara, primary, Brors, Benedikt, primary, Stenzinger, Albrecht, primary, Schröck, Evelin, primary, Hübschmann, Daniel, primary, Weichert, Wilko, primary, Glimm, Hanno, primary, and Fröhling, Stefan, primary

Published
2023
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17. Supplementary Tables S1-S7 from Comprehensive Genomic and Transcriptomic Analysis for Guiding Therapeutic Decisions in Patients with Rare Cancers

Author

Horak, Peter, primary, Heining, Christoph, primary, Kreutzfeldt, Simon, primary, Hutter, Barbara, primary, Mock, Andreas, primary, Hüllein, Jennifer, primary, Fröhlich, Martina, primary, Uhrig, Sebastian, primary, Jahn, Arne, primary, Rump, Andreas, primary, Gieldon, Laura, primary, Möhrmann, Lino, primary, Hanf, Dorothea, primary, Teleanu, Veronica, primary, Heilig, Christoph E., primary, Lipka, Daniel B., primary, Allgäuer, Michael, primary, Ruhnke, Leo, primary, Laßmann, Andreas, primary, Endris, Volker, primary, Neumann, Olaf, primary, Penzel, Roland, primary, Beck, Katja, primary, Richter, Daniela, primary, Winter, Ulrike, primary, Wolf, Stephan, primary, Pfütze, Katrin, primary, Geörg, Christina, primary, Meißburger, Bettina, primary, Buchhalter, Ivo, primary, Augustin, Marinela, primary, Aulitzky, Walter E., primary, Hohenberger, Peter, primary, Kroiss, Matthias, primary, Schirmacher, Peter, primary, Schlenk, Richard F., primary, Keilholz, Ulrich, primary, Klauschen, Frederick, primary, Folprecht, Gunnar, primary, Bauer, Sebastian, primary, Siveke, Jens Thomas, primary, Brandts, Christian H., primary, Kindler, Thomas, primary, Boerries, Melanie, primary, Illert, Anna L., primary, von Bubnoff, Nikolas, primary, Jost, Philipp J., primary, Spiekermann, Karsten, primary, Bitzer, Michael, primary, Schulze-Osthoff, Klaus, primary, von Kalle, Christof, primary, Klink, Barbara, primary, Brors, Benedikt, primary, Stenzinger, Albrecht, primary, Schröck, Evelin, primary, Hübschmann, Daniel, primary, Weichert, Wilko, primary, Glimm, Hanno, primary, and Fröhling, Stefan, primary

Published
2023
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18. Supplementary Figures S1-S10 from Comprehensive Genomic and Transcriptomic Analysis for Guiding Therapeutic Decisions in Patients with Rare Cancers

Author

Horak, Peter, primary, Heining, Christoph, primary, Kreutzfeldt, Simon, primary, Hutter, Barbara, primary, Mock, Andreas, primary, Hüllein, Jennifer, primary, Fröhlich, Martina, primary, Uhrig, Sebastian, primary, Jahn, Arne, primary, Rump, Andreas, primary, Gieldon, Laura, primary, Möhrmann, Lino, primary, Hanf, Dorothea, primary, Teleanu, Veronica, primary, Heilig, Christoph E., primary, Lipka, Daniel B., primary, Allgäuer, Michael, primary, Ruhnke, Leo, primary, Laßmann, Andreas, primary, Endris, Volker, primary, Neumann, Olaf, primary, Penzel, Roland, primary, Beck, Katja, primary, Richter, Daniela, primary, Winter, Ulrike, primary, Wolf, Stephan, primary, Pfütze, Katrin, primary, Geörg, Christina, primary, Meißburger, Bettina, primary, Buchhalter, Ivo, primary, Augustin, Marinela, primary, Aulitzky, Walter E., primary, Hohenberger, Peter, primary, Kroiss, Matthias, primary, Schirmacher, Peter, primary, Schlenk, Richard F., primary, Keilholz, Ulrich, primary, Klauschen, Frederick, primary, Folprecht, Gunnar, primary, Bauer, Sebastian, primary, Siveke, Jens Thomas, primary, Brandts, Christian H., primary, Kindler, Thomas, primary, Boerries, Melanie, primary, Illert, Anna L., primary, von Bubnoff, Nikolas, primary, Jost, Philipp J., primary, Spiekermann, Karsten, primary, Bitzer, Michael, primary, Schulze-Osthoff, Klaus, primary, von Kalle, Christof, primary, Klink, Barbara, primary, Brors, Benedikt, primary, Stenzinger, Albrecht, primary, Schröck, Evelin, primary, Hübschmann, Daniel, primary, Weichert, Wilko, primary, Glimm, Hanno, primary, and Fröhling, Stefan, primary

Published
2023
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19. Supplementary Methods from Comprehensive Genomic and Transcriptomic Analysis for Guiding Therapeutic Decisions in Patients with Rare Cancers

Author

Horak, Peter, primary, Heining, Christoph, primary, Kreutzfeldt, Simon, primary, Hutter, Barbara, primary, Mock, Andreas, primary, Hüllein, Jennifer, primary, Fröhlich, Martina, primary, Uhrig, Sebastian, primary, Jahn, Arne, primary, Rump, Andreas, primary, Gieldon, Laura, primary, Möhrmann, Lino, primary, Hanf, Dorothea, primary, Teleanu, Veronica, primary, Heilig, Christoph E., primary, Lipka, Daniel B., primary, Allgäuer, Michael, primary, Ruhnke, Leo, primary, Laßmann, Andreas, primary, Endris, Volker, primary, Neumann, Olaf, primary, Penzel, Roland, primary, Beck, Katja, primary, Richter, Daniela, primary, Winter, Ulrike, primary, Wolf, Stephan, primary, Pfütze, Katrin, primary, Geörg, Christina, primary, Meißburger, Bettina, primary, Buchhalter, Ivo, primary, Augustin, Marinela, primary, Aulitzky, Walter E., primary, Hohenberger, Peter, primary, Kroiss, Matthias, primary, Schirmacher, Peter, primary, Schlenk, Richard F., primary, Keilholz, Ulrich, primary, Klauschen, Frederick, primary, Folprecht, Gunnar, primary, Bauer, Sebastian, primary, Siveke, Jens Thomas, primary, Brandts, Christian H., primary, Kindler, Thomas, primary, Boerries, Melanie, primary, Illert, Anna L., primary, von Bubnoff, Nikolas, primary, Jost, Philipp J., primary, Spiekermann, Karsten, primary, Bitzer, Michael, primary, Schulze-Osthoff, Klaus, primary, von Kalle, Christof, primary, Klink, Barbara, primary, Brors, Benedikt, primary, Stenzinger, Albrecht, primary, Schröck, Evelin, primary, Hübschmann, Daniel, primary, Weichert, Wilko, primary, Glimm, Hanno, primary, and Fröhling, Stefan, primary

Published
2023
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20. Biallelic TET2 mutations confer sensitivity to 5'-azacitidine in acute myeloid leukemia.

Author

Stölzel, Friedrich, Stölzel, Friedrich, Fordham, Sarah E, Nandana, Devi, Lin, Wei-Yu, Blair, Helen, Elstob, Claire, Bell, Hayden L, Mohr, Brigitte, Ruhnke, Leo, Kunadt, Desiree, Dill, Claudia, Allsop, Daniel, Piddock, Rachel, Soura, Emmanouela-Niki, Park, Catherine, Fadly, Mohd, Rahman, Thahira, Alharbi, Abrar, Wobus, Manja, Altmann, Heidi, Röllig, Christoph, Wagenführ, Lisa, Jones, Gail L, Menne, Tobias, Jackson, Graham H, Marr, Helen J, Fitzgibbon, Jude, Onel, Kenan, Meggendorfer, Manja, Robinson, Amber, Bziuk, Zuzanna, Bowes, Emily, Heidenreich, Olaf, Haferlach, Torsten, Villar, Sara, Ariceta, Beñat, Diaz, Rosa Ayala, Altschuler, Steven J, Wu, Lani F, Prosper, Felipe, Montesinos, Pau, Martinez-Lopez, Joaquin, Bornhäuser, Martin, Allan, James M, Stölzel, Friedrich, Stölzel, Friedrich, Fordham, Sarah E, Nandana, Devi, Lin, Wei-Yu, Blair, Helen, Elstob, Claire, Bell, Hayden L, Mohr, Brigitte, Ruhnke, Leo, Kunadt, Desiree, Dill, Claudia, Allsop, Daniel, Piddock, Rachel, Soura, Emmanouela-Niki, Park, Catherine, Fadly, Mohd, Rahman, Thahira, Alharbi, Abrar, Wobus, Manja, Altmann, Heidi, Röllig, Christoph, Wagenführ, Lisa, Jones, Gail L, Menne, Tobias, Jackson, Graham H, Marr, Helen J, Fitzgibbon, Jude, Onel, Kenan, Meggendorfer, Manja, Robinson, Amber, Bziuk, Zuzanna, Bowes, Emily, Heidenreich, Olaf, Haferlach, Torsten, Villar, Sara, Ariceta, Beñat, Diaz, Rosa Ayala, Altschuler, Steven J, Wu, Lani F, Prosper, Felipe, Montesinos, Pau, Martinez-Lopez, Joaquin, Bornhäuser, Martin, and Allan, James M

Abstract

Precision medicine can significantly improve outcomes for patients with cancer, but implementation requires comprehensive characterization of tumor cells to identify therapeutically exploitable vulnerabilities. Here, we describe somatic biallelic TET2 mutations in an elderly patient with acute myeloid leukemia (AML) that was chemoresistant to anthracycline and cytarabine but acutely sensitive to 5'-azacitidine (5'-Aza) hypomethylating monotherapy, resulting in long-term morphological remission. Given the role of TET2 as a regulator of genomic methylation, we hypothesized that mutant TET2 allele dosage affects response to 5'-Aza. Using an isogenic cell model system and an orthotopic mouse xenograft, we demonstrate that biallelic TET2 mutations confer sensitivity to 5'-Aza compared with cells with monoallelic mutations. Our data argue in favor of using hypomethylating agents for chemoresistant disease or as first-line therapy in patients with biallelic TET2-mutated AML and demonstrate the importance of considering mutant allele dosage in the implementation of precision medicine for patients with cancer.

Published
2023

21. Midostaurin in addition to intensive chemotherapy in acute myeloid leukemia with t(8;21) and KIT and/or FLT3-ITD mutations: results of the SAL MIDOKIT trial

Author

Ruhnke, Leo, primary, Röllig, Christoph, additional, Herold, Sylvia, additional, Sauer, Tim, additional, Brandts, Christian H, additional, Steffen, Björn, additional, Schäfer-Eckart, Kerstin, additional, Krause, Stefan W, additional, Hänel, Mathias, additional, Reichle, Albrecht, additional, Scholl, Sebastian, additional, Neubauer, Andreas, additional, Mikesch, Jan-Henrik, additional, Schetelig, Johannes, additional, Stölzel, Friedrich, additional, Kramer, Michael, additional, Haake, Annett, additional, Frimmel, Julia, additional, Krämer, Alwin, additional, Schlenk, Richard, additional, Platzbecker, Uwe, additional, Serve, Hubert, additional, Baldus, Claudia D, additional, Müller-Tidow, Carsten, additional, Aust, Daniela, additional, Bornhäuser, Martin, additional, Ehninger, Gerhard, additional, and Thiede, Christian, additional

Published
2023
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22. Next Generation Biobanking: Employing a Robotic System for Automated Mononuclear Cell Isolation

Author

Fuchs, Yannick F., primary, Brunner, Jonathan, additional, Weigelt, Marc, additional, Schieferdecker, Anja, additional, Morgenstern, Robert, additional, Sturm, Andrea, additional, Winter, Boris, additional, Jambor, Helena, additional, Stölzel, Friedrich, additional, Ruhnke, Leo, additional, von Bonin, Malte, additional, Rücker-Braun, Elke, additional, Heidenreich, Falk, additional, Fuchs, Anke, additional, Bonifacio, Ezio, additional, Bornhäuser, Martin, additional, Poitz, David M., additional, and Altmann, Heidi, additional

Published
2023
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23. Biallelic TET2 mutations confer sensitivity to 5′-azacitidine in acute myeloid leukemia

Author

Stölzel, Friedrich, primary, Fordham, Sarah E., additional, Nandana, Devi, additional, Lin, Wei-Yu, additional, Blair, Helen, additional, Elstob, Claire, additional, Bell, Hayden L., additional, Mohr, Brigitte, additional, Ruhnke, Leo, additional, Kunadt, Desiree, additional, Dill, Claudia, additional, Allsop, Daniel, additional, Piddock, Rachel, additional, Soura, Emmanouela-Niki, additional, Park, Catherine, additional, Fadly, Mohd, additional, Rahman, Thahira, additional, Alharbi, Abrar, additional, Wobus, Manja, additional, Altmann, Heidi, additional, Röllig, Christoph, additional, Wagenführ, Lisa, additional, Jones, Gail L., additional, Menne, Tobias, additional, Jackson, Graham H., additional, Marr, Helen J., additional, Fitzgibbon, Jude, additional, Onel, Kenan, additional, Meggendorfer, Manja, additional, Robinson, Amber, additional, Bziuk, Zuzanna, additional, Bowes, Emily, additional, Heidenreich, Olaf, additional, Haferlach, Torsten, additional, Villar, Sara, additional, Ariceta, Beñat, additional, Diaz, Rosa Ayala, additional, Altschuler, Steven J., additional, Wu, Lani F., additional, Prosper, Felipe, additional, Montesinos, Pau, additional, Martinez-Lopez, Joaquin, additional, Bornhäuser, Martin, additional, and Allan, James M., additional

Published
2023
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24. Prevalence, Clinical and Molecular Features, and Prognostic Value of Tetraploidy/Near-Tetraploidy in Patients with Acute Myeloid Leukemia

Author

Ruhnke, Leo, primary, Frimmel, Julia, additional, Röllig, Christoph, additional, Mohr, Brigitte, additional, Altmann, Heidi, additional, Poitz, David, additional, Zukunft, Sven, additional, Schranz, Katrin, additional, Vosberg, Sebastian, additional, Spiekermann, Karsten, additional, von Bergwelt, Michael, additional, Jost, Edgar, additional, Dressler, Sabine, additional, Schäfer-Eckart, Kerstin, additional, Chavakis, Triantafyllos, additional, Aust, Daniela, additional, Jöhrens, Korinna, additional, Baretton, Gustavo, additional, Bornhäuser, Martin, additional, Greif, Philipp A., additional, Stölzel, Friedrich, additional, Herold, Sylvia, additional, and Wagenführ, Lisa, additional

Published
2022
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25. Venetoclax Plus High-Dose Cytarabine and Mitoxantrone As Feasible and Effective Novel Treatment for Relapsed AML: Results of the Phase-I SAL Relax Trial

Author

Röllig, Christoph, primary, Fransecky, Lars, additional, Hanoun, Maher, additional, Steffen, Björn, additional, Kraus, Sabrina, additional, Schliemann, Christoph, additional, Haake, Annett, additional, Fiebig, Frank, additional, Zukunft, Sven, additional, Alakel, Nael, additional, Middeke, Jan Moritz, additional, Bornhaeuser, Martin, additional, Stoelzel, Friedrich, additional, Schetelig, Johannes, additional, Ruhnke, Leo, additional, Kramer, Michael, additional, Von Bonin, Malte, additional, Röhnert, Maximilian Alexander, additional, Oelschlägel, Uta, additional, Baldus, Claudia D., additional, Serve, Hubert, additional, and Wermke, Martin, additional

Published
2022
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26. Abstract CT188: ICT01, an anti-butyrophilin 3A targeted mAb activating g9d2 T cells, induces immune remodeling of the tumor microenvironment and clinical responses in combination with pembrolizumab in patients with advanced solid tumors who failed prior checkpoint inhibitor therapy: EVICTION Trial

Author

Champiat, Stephane, primary, Wermke, Martin, additional, de Bono, Johann, additional, Marabelle, Aurelien, additional, Jungels, Christiane, additional, Vicier, Cécile, additional, Vey, Norbert, additional, List, Catrin, additional, Wetzko, Katrin, additional, Ruhnke, Leo, additional, Garralda, Elena, additional, de Aguiar, Vladimir Galvão, additional, LoRusso, Patricia, additional, Kotecki, Nuria, additional, De Gassart, Aude, additional, Valentin, Emmanuel, additional, Brune, Patrick, additional, Iché, Marina, additional, Leparquier, Céline, additional, Olive, Daniel, additional, and Frohna, Paul, additional

Published
2022
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27. Intensified cytarabine dose during consolidation in AML patients under 65 years is not associated with survival benefit: real-world data from the German SAL-AML registry

Author

Hanoun, Maher, primary, Ruhnke, Leo, additional, Kramer, Michael, additional, Hanoun, Christine, additional, Schäfer-Eckart, Kerstin, additional, Steffen, Björn, additional, Sauer, Tim, additional, Krause, Stefan, additional, Schliemann, Christoph, additional, Mikesch, Jan-Henrik, additional, Kaufmann, Martin, additional, Haenel, Mathias, additional, Jost, Edgar, additional, Bruemmendorf, Tim, additional, Fransecky, LArs, additional, Kraus, Sabrina, additional, Einsele, Hermann, additional, Niemann, Dirk, additional, Neubauer, Andreas, additional, Kullmer, Johannes, additional, Seggewiss-Bernhard, Ruth, additional, Goerner, Martin, additional, Held, Gerhard, additional, Kaiser, Ulrich, additional, Scholl, Sebastian, additional, Hochhaus, Andreas, additional, Reinhardt, Hans, additional, Platzbecker, Uwe, additional, Baldus, Claudia, additional, Müller-Tidow, Carsten, additional, Bornhäuser, Martin, additional, Serve, Hubert, additional, and Röllig, Christoph, additional

Published
2022
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29. sj-docx-1-tah-10.1177_20406207221115005 – Supplemental material for Spatial heterogeneity and differential treatment response of acute myeloid leukemia and relapsed/refractory extramedullary disease after allogeneic hematopoietic cell transplantation

Author

Kunadt, Desiree, Herold, Sylvia, Poitz, David, Wagenführ, Lisa, Kretschmann, Theresa, Sockel, Katja, Ruhnke, Leo, Brückner, Stefan, Sommer, Ulrich, Meier, Frieder, Röllig, Christoph, von Bonin, Malte, Thiede, Christian, Schetelig, Johannes, Bornhäuser, Martin, and Stölzel, Friedrich

Subjects
FOS: Clinical medicine, Cardiology, 111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified, 111299 Oncology and Carcinogenesis not elsewhere classified
Abstract

Supplemental material, sj-docx-1-tah-10.1177_20406207221115005 for Spatial heterogeneity and differential treatment response of acute myeloid leukemia and relapsed/refractory extramedullary disease after allogeneic hematopoietic cell transplantation by Desiree Kunadt, Sylvia Herold, David Poitz, Lisa Wagenführ, Theresa Kretschmann, Katja Sockel, Leo Ruhnke, Stefan Brückner, Ulrich Sommer, Frieder Meier, Christoph Röllig, Malte von Bonin, Christian Thiede, Johannes Schetelig, Martin Bornhäuser and Friedrich Stölzel in Therapeutic Advances in Hematology

Published
2022
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30. Genome-wide association study identifies susceptibility loci for acute myeloid leukemia (vol 13, 2, 2022)

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, Bornhauser, Martin, Rollig, Christoph, Altmann, Heidi, Ruhnke, Leo, Kunadt, Desiree, Wagenfuhr, Lisa, Cordell, Heather J., Darlay, Rebecca, Andersen, Mette K., Fontana, Maria C., Martinelli, Giovanni, Marconi, Giovanni, Sanz, Miguel A., Cervera, Jose, Gomez-Segui, Ines, Cluzeau, Thomas, Moreilhon, Chimene, Raynaud, Sophie, Sill, Heinz, Voso, Maria Teresa, Lo-Coco, Francesco, Dombret, Herve, 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, Krizsan, Szilvia, Bodor, Csaba, Stolzel, Friedrich, Onel, Kenan, and Allan, James M.

Published
2022

31. Spatial heterogeneity and differential treatment response of acute myeloid leukemia and relapsed/refractory extramedullary disease after allogeneic hematopoietic cell transplantation

Author

Kunadt, Desiree, primary, Herold, Sylvia, additional, Poitz, David, additional, Wagenführ, Lisa, additional, Kretschmann, Theresa, additional, Sockel, Katja, additional, Ruhnke, Leo, additional, Brückner, Stefan, additional, Sommer, Ulrich, additional, Meier, Frieder, additional, Röllig, Christoph, additional, von Bonin, Malte, additional, Thiede, Christian, additional, Schetelig, Johannes, additional, Bornhäuser, Martin, additional, and Stölzel, Friedrich, additional

Published
2022
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33. Long-Term Mixed Chimerism After Ex Vivo/In Vivo T Cell-Depleted Allogeneic Hematopoietic Cell Transplantation in Patients With Myeloid Neoplasms

Author

Ruhnke, Leo, primary, Stölzel, Friedrich, additional, Oelschlägel, Uta, additional, von Bonin, Malte, additional, Sockel, Katja, additional, Middeke, Jan Moritz, additional, Röllig, Christoph, additional, Jöhrens, Korinna, additional, Schetelig, Johannes, additional, Thiede, Christian, additional, and Bornhäuser, Martin, additional

Published
2021
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34. A Phase I Trial of the Antibody-Cytokine Fusion Protein F16IL2 in Combination with Anti-CD33 Immunotherapy for Posttransplant AML Relapse

Author

Berdel, Andrew F., primary, Rollig, Christoph, additional, Wermke, Martin, additional, Angenendt, Linus, additional, Ruhnke, Leo, additional, Mikesch, Jan-Henrik, additional, Hemmerle, Teresa, additional, Wethmar, Klaus, additional, Kessler, Torsten, additional, Gerwing, Mirjam, additional, Hescheler, Daniel, additional, Schäfers, Michael, additional, Hartmann, Wolfgang, additional, Altvater, Bianca, additional, Rossig, Claudia, additional, Lenz, Georg, additional, Stelljes, Matthias, additional, Rueter, Bjoern, additional, Neri, Dario, additional, Berdel, Wolfgang E., additional, and Schliemann, Christoph, additional

Published
2021
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35. Diagnostic Red Blood Cell Distribution Width As a Prognostic Factor in Acute Myeloid Leukemia

Author

Vucinic, Vladan, primary, Ruhnke, Leo, additional, Sockel, Katja, additional, Röhnert, Maximilian Alexander, additional, Backhaus, Donata, additional, Brauer, Dominic, additional, Franke, Georg-Nikolaus, additional, Niederwieser, Dietger, additional, Bornhäuser, Martin, additional, Rollig, Christoph, additional, Platzbecker, Uwe, additional, Schwind, Sebastian, additional, and Jentzsch, Madlen, additional

Published
2021
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36. Intensified Cytarabine Dose during Consolidation Therapy in AML Patients Under 65 Years Is Not Associated with Survival Benefit

Author

Hanoun, Maher, primary, Ruhnke, Leo, additional, Kramer, Michael, additional, Schäfer-Eckhard, Kerstin, additional, Steffen, Björn, additional, Sauer, Tim, additional, Krause, Stefan W., additional, Schliemann, Christoph, additional, Kaufmann, Martin, additional, Haenel, Mathias, additional, Jost, Edgar, additional, Brummendorf, Tim H, additional, Fransecky, Lars, additional, Kraus, Sabrina, additional, Einsele, Hermann, additional, Niemann, Dirk, additional, Neubauer, Andreas, additional, Kullmer, Johannes, additional, Seggewiss-Bernhard, Ruth, additional, Goerner, Martin, additional, Held, Gerhard, additional, Kaiser, Ulrich, additional, Scholl, Sebastian, additional, Reinhardt, Hans Christian, additional, Platzbecker, Uwe, additional, Baldus, Claudia D., additional, Mueller-Tidow, Carsten, additional, Bornhaeuser, Martin, additional, Serve, Hubert, additional, and Rollig, Christoph, additional

Published
2021
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37. Impact of Body Mass Index on Patient Outcome in Acute Myeloid Leukemia Patients Receiving Intensive Induction Therapy: A Real-World Registry Experience

Author

Enssle, Julius Christoph, primary, Wolf, Sebastian, additional, Scheich, Sebastian, additional, Weber, Sarah, additional, Kramer, Michael, additional, Ruhnke, Leo, additional, Schliemann, Christoph, additional, Mikesch, Jan-Henrik, additional, Krause, Stefan W., additional, Sauer, Tim, additional, Hanoun, Maher, additional, Reinhardt, Hans Christian, additional, Kraus, Sabrina, additional, Kaufmann, Martin, additional, Haenel, Mathias, additional, Fransecky, Lars, additional, Burchert, Andreas, additional, Neubauer, Andreas, additional, Crysandt, Martina, additional, Jost, Edgar, additional, Niemann, Dirk, additional, Schäfer-Eckhard, Kerstin, additional, Held, Gerhard, additional, Kaiser, Ulrich, additional, Wass, Maxi, additional, Schaich, Markus, additional, Müller-Tidow, Carsten, additional, Platzbecker, Uwe, additional, Baldus, Claudia D., additional, Bornhäuser, Martin, additional, Rollig, Christoph, additional, Serve, Hubert, additional, and Steffen, Björn, additional

Published
2021
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38. Case Report: ANXA2 Associated Life-Threatening Coagulopathy With Hyperfibrinolysis in a Patient With Non-APL Acute Myeloid Leukemia

Author

Ruhnke, Leo, Stölzel, Friedrich, Wagenführ, Lisa, Altmann, Heidi, Platzbecker, Uwe, Herold, Sylvia, Rump, Andreas, Schröck, Evelin, Bornhäuser, Martin, Schetelig, Johannes, and von Bonin, Malte

Subjects
Cancer Research, Case Report, acute promyelocytic leukemia, acute myeloid leukemia, acute promyelocytic leukemia, acute myeloid leukemia, hyperfibrinolysis, disseminated intravascular coagulation, coagulopathy, ANXA2, PDPN, WES, PDPN, coagulopathy, Oncology, immune system diseases, hemic and lymphatic diseases, ANXA2, hyperfibrinolysis, WES, ddc:610, neoplasms, disseminated intravascular coagulation
Abstract

Patients with acute promyelocytic leukemia (APL) often present with potentially life-threatening hemorrhagic diathesis. The underlying pathomechanisms of APL-associated coagulopathy are complex. However, two pathways considered to be APL-specific had been identified: 1) annexin A2 (ANXA2)-associated hyperfibrinolysis and 2) podoplanin (PDPN)-mediated platelet activation and aggregation. In contrast, since disseminated intravascular coagulation (DIC) is far less frequent in patients with non-APL acute myeloid leukemia (AML), the pathophysiology of AML-associated hemorrhagic disorders is not well understood. Furthermore, the potential threat of coagulopathy in non-APL AML patients may be underestimated. Herein, we report a patient with non-APL AML presenting with severe coagulopathy with hyperfibrinolysis. Since his clinical course resembled a prototypical APL-associated hemorrhagic disorder, we hypothesized pathophysiological similarities. Performing multiparametric flow cytometry (MFC) and immunofluorescence imaging (IF) studies, we found the patient’s bone-marrow mononuclear cells (BM-MNC) to express ANXA2 - a biomarker previously thought to be APL-specific. In addition, whole-exome sequencing (WES) on sorted BM-MNC (leukemia-associated immunophenotype (LAIP)1: ANXAlo, LAIP2: ANXAhi) demonstrated high intra-tumor heterogeneity. Since ANXA2 regulation is not well understood, further research to determine the coagulopathy-initiating events in AML and APL is indicated. Moreover, ANXA2 and PDPN MFC assessment as a tool to determine the risk of life-threatening DIC in AML and APL patients should be evaluated.

Published
2021

39. Genome-wide association study identifies susceptibility loci for acute myeloid leukemia

Author

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

Published
2021
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40. Biallelic TET2 mutation sensitizes to 5’-azacitidine in acute myeloid leukemia

Author

Stölzel, Friedrich, primary, Fordham, Sarah E., additional, Lin, Wei-Yu, additional, Blair, Helen, additional, Elstob, Claire, additional, Nandana, Devi, additional, Mohr, Brigitte, additional, Ruhnke, Leo, additional, Kunadt, Desiree, additional, Dill, Claudia, additional, Allsop, Daniel, additional, Piddock, Rachel, additional, Soura, Emmanouela-Niki, additional, Park, Catherine, additional, Fadly, Mohd, additional, Rahman, Thahira, additional, Alharbi, Abrar, additional, Wobus, Manja, additional, Altmann, Heidi, additional, Röllig, Christoph, additional, Wagenführ, Lisa, additional, Jones, Gail L., additional, Menne, Tobias, additional, Jackson, Graham H., additional, Marr, Helen J., additional, Fitzgibbon, Jude, additional, Onel, Kenan, additional, Meggendorfer, Manja, additional, Heidenreich, Olaf, additional, Haferlach, Torsten, additional, Villar, Sara, additional, Ariceta, Beñat, additional, Diaz, Rosa Ayala, additional, Prosper, Felipe, additional, Montesinos, Pau, additional, Martinez-Lopez, Joaquin, additional, Bornhäuser, Martin, additional, and Allan, James M., additional

Published
2021
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41. Comprehensive Genomic and Transcriptomic Analysis for Guiding Therapeutic Decisions in Patients with Rare Cancers

Author

Horak, Peter, primary, Heining, Christoph, additional, Kreutzfeldt, Simon, additional, Hutter, Barbara, additional, Mock, Andreas, additional, Hüllein, Jennifer, additional, Fröhlich, Martina, additional, Uhrig, Sebastian, additional, Jahn, Arne, additional, Rump, Andreas, additional, Gieldon, Laura, additional, Möhrmann, Lino, additional, Hanf, Dorothea, additional, Teleanu, Veronica, additional, Heilig, Christoph E., additional, Lipka, Daniel B., additional, Allgäuer, Michael, additional, Ruhnke, Leo, additional, Laßmann, Andreas, additional, Endris, Volker, additional, Neumann, Olaf, additional, Penzel, Roland, additional, Beck, Katja, additional, Richter, Daniela, additional, Winter, Ulrike, additional, Wolf, Stephan, additional, Pfütze, Katrin, additional, Geörg, Christina, additional, Meißburger, Bettina, additional, Buchhalter, Ivo, additional, Augustin, Marinela, additional, Aulitzky, Walter E., additional, Hohenberger, Peter, additional, Kroiss, Matthias, additional, Schirmacher, Peter, additional, Schlenk, Richard F., additional, Keilholz, Ulrich, additional, Klauschen, Frederick, additional, Folprecht, Gunnar, additional, Bauer, Sebastian, additional, Siveke, Jens Thomas, additional, Brandts, Christian H., additional, Kindler, Thomas, additional, Boerries, Melanie, additional, Illert, Anna L., additional, von Bubnoff, Nikolas, additional, Jost, Philipp J., additional, Spiekermann, Karsten, additional, Bitzer, Michael, additional, Schulze-Osthoff, Klaus, additional, von Kalle, Christof, additional, Klink, Barbara, additional, Brors, Benedikt, additional, Stenzinger, Albrecht, additional, Schröck, Evelin, additional, Hübschmann, Daniel, additional, Weichert, Wilko, additional, Glimm, Hanno, additional, and Fröhling, Stefan, additional

Published
2021
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42. Secondary-Type Mutations Do Not Impact the Favorable Outcome of NPM1-Mutated Acute Myeloid Leukemia Patients - Results from a Large Cohort of Intensively Treated Patients

Author

Bill, Marius, Eckardt, Jan-Niklas, Rausch, Christian, Metzeler, Klaus H, Spiekermann, Karsten, Stasik, Sebastian, Sauer, Tim, Scholl, Sebastian, Hochhaus, Andreas, Crysandt, Martina, Brümmendorf, Tim H., Krug, Utz, Wörmann, Bernhard, Hiddemann, Wolfgang, Görlich, Dennis, Sauerland, Maria Cristina, Steffen, Björn, Einsele, Hermann, Neubauer, Andreas, Burchert, Andreas, Schaefer-Eckart, Kerstin, Berdel, Wolfgang E., Schliemann, Christoph, Krause, Stefan W., Hanel, Mathias, Hanoun, Maher, Kaufmann, Martin, Fransecky, Lars, Braess, Jan, Ruhnke, Leo, Schetelig, Johannes, Middeke, Jan Moritz, Serve, Hubert, Baldus, Claudia D, Platzbecker, Uwe, Müller-Tidow, Carsten, Bornhäuser, Martin, Herold, Tobias, Thiede, Christian, and Röllig, Christoph

Published
2023
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43. 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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44. Secondary-type mutations do not impact outcome in NPM1-mutated acute myeloid leukemia – implications for the European leukemia net risk classification

Author

Eckardt, Jan-Niklas, Bill, Marius, Rausch, Christian, Metzeler, Klaus, Spiekermann, Karsten, Stasik, Sebastian, Sauer, Tim, Scholl, Sebastian, Hochhaus, Andreas, Crysandt, Martina, Brümmendorf, Tim H., Krug, Utz, Wörmann, Bernhard, Hiddemann, Wolfgang, Görlich, Dennis, Sauerland, Cristina, Steffen, Björn, Einsele, Hermann, Neubauer, Andreas, Burchert, Andreas, Schäfer-Eckart, Kerstin, Berdel, Wolfgang E., Schliemann, Christoph, Krause, Stefan W., Hänel, Mathias, Hanoun, Maher, Kaufmann, Martin, Fransecky, Lars, Braess, Jan, Ruhnke, Leo, Schetelig, Johannes, Middeke, Jan Moritz, Serve, Hubert, Baldus, Claudia D., Platzbecker, Uwe, Müller-Tidow, Carsten, Bornhäuser, Martin, Herold, Tobias, Thiede, Christian, and Röllig, Christoph

Published
2023
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45. Long-Term Mixed Chimerism After Ex Vivo / In Vivo T Cell-Depleted Allogeneic Hematopoietic Cell Transplantation in Patients With Myeloid Neoplasms.

Author

Ruhnke, Leo, Stölzel, Friedrich, Oelschlägel, Uta, von Bonin, Malte, Sockel, Katja, Middeke, Jan Moritz, Röllig, Christoph, Jöhrens, Korinna, Schetelig, Johannes, Thiede, Christian, and Bornhäuser, Martin

Subjects
HEMATOPOIETIC stem cell transplantation, ACUTE diseases, MONONUCLEAR leukocytes, REGULATORY T cells, CHIMERISM, MICROSATELLITE repeats
Abstract

In patients who have undergone allogeneic hematopoietic cell transplantation (HCT), myeloid mixed donor chimerism (MC) is a risk factor for disease relapse. In contrast, several studies found favorable outcome in patients with lymphoid MC. Thus far, most studies evaluating MC focused on a short-term follow-up period. Here, we report the first case series of long-term survivors with MC. We screened 1,346 patients having undergone HCT for myeloid neoplasms at our center from 1996 to 2016; 443 patients with data on total peripheral blood mononuclear cells (PBMC)/CD4+/CD34+ short tandem repeat (STR) donor chimerism (DC) and follow-up ≥24 months post-HCT were included. We identified 10 patients with long-term MC (PBMC DC <95% at ≥12 months post-HCT). Median follow-up was 11 years. All patients had received combined ex vivo/in vivo T cell-depleted (TCD) peripheral blood stem cells; none experienced ≥grade 2 acute graft-versus-host disease (GVHD). The mean total PBMC, CD4+, and CD34+ DC of all patients were 95.88%, 85.84%, and 90.15%, respectively. Reduced-intensity conditioning (RIC) was associated with a trend to lower mean total DC. Of note, two patients who experienced relapse had lower CD34+ DC but higher CD4+ DC as compared with patients in continuous remission. Bone marrow evaluation revealed increased CD4+/FOXP3+ cells in patients with MC, which might indicate expansion of regulatory T cells (Tregs). Our results support known predictive factors associated with MC such as RIC and TCD, promote the value of CD34+ MC as a potential predictor of relapse, highlight the potential association of CD4+ MC with reduced risk of GVHD, and indicate a possible role of Tregs in the maintenance of immune tolerance post-HCT. [ABSTRACT FROM AUTHOR]

Published
2021
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46. Mutant TET2 Allele Dosage Affects Response to 5-Azacitidine in Acute Myeloid Leukemia

Author

Stoelzel, Friedrich, primary, Fordham, Sarah Elizabeth, primary, Lin, Wei Yu, primary, Blair, Helen, primary, Ruhnke, Leo, primary, Kunadt, Desireé, primary, Mohr, Brigitte, primary, Elstob, Claire, primary, Allsop, Daniel, primary, Nandana, Devi, primary, Soura, Emmanouela-Niki, primary, Park, Catherine, primary, Fadly, Mohd, primary, Rahman, Thahira, primary, Heidenreich, Olaf, primary, Altmann, Heidi, primary, Jones, Gail, primary, Menne, Tobias, primary, Wobus, Manja, primary, Jackson, Graham, primary, Marr, Helen, primary, Onel, Kenan, primary, Meggendorfer, Manja, primary, Haferlach, Torsten, primary, Bornhäuser, Martin, primary, and Allan, James M., primary

Published
2019
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47. New automatic quantification method of immunofluorescence and histochemistry in whole histological sections

Author

Kessel, Friederike, primary, Steglich, Anne, additional, Tschongov, Todor, additional, Gembardt, Florian, additional, Ruhnke, Leo, additional, Stumpf, Julian, additional, Behrendt, Rayk, additional, Cohrs, Christian, additional, Kopaliani, Irakli, additional, Todorov, Vladimir, additional, Gerlach, Michael, additional, and Hugo, Christian, additional

Published
2019
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49. Venetoclax Plus High-Dose Cytarabine and Mitoxantrone (HAM-Ven) As Salvage Treatment for Relapsed/Refractory AML: Updated Results of the Phase-I/II SAL Relax Trial

Author

Ruhnke, Leo, Schliemann, Christoph, Mikesch, Jan-Henrik, Stelljes, Matthias, Fransecky, Lars, Steffen, Björn, Kaufmann, Martin, Burchert, Andreas, Rank, Andreas, Hanoun, Maher, Höllein, Alexander, Kraus, Sabrina, Hänel, Mathias, Schäfer-Eckart, Kerstin, Haake, Annett, Fiebig, Frank, Zukunft, Sven, Middeke, Jan Moritz, Kunadt, Désirée, Schetelig, Johannes, von Bonin, Malte, Röhnert, Maximilian Alexander, Oelschlägel, Uta, Stölzel, Friedrich, Baldus, Claudia D, Serve, Hubert, Wermke, Martin, Bornhäuser, Martin, and Röllig, Christoph

Abstract

Background

Published
2023
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50. Mutant TET2Allele Dosage Affects Response to 5-Azacitidine in Acute Myeloid Leukemia

Author

Stoelzel, Friedrich, Fordham, Sarah Elizabeth, Lin, Wei Yu, Blair, Helen, Ruhnke, Leo, Kunadt, Desireé, Mohr, Brigitte, Elstob, Claire, Allsop, Daniel, Nandana, Devi, Soura, Emmanouela-Niki, Park, Catherine, Fadly, Mohd, Rahman, Thahira, Heidenreich, Olaf, Altmann, Heidi, Jones, Gail, Menne, Tobias, Wobus, Manja, Jackson, Graham, Marr, Helen, Onel, Kenan, Meggendorfer, Manja, Haferlach, Torsten, Bornhäuser, Martin, and Allan, James M.

Abstract

Personalised medicine is predicted to significantly improve outcomes for cancer patients, but implementation requires comprehensive genetic characterisation of malignant cells to identify therapeutically exploitable vulnerabilities. Using an isogenic cell model system with CRISPR-inactivated TET2in HEL acute myeloid leukemia (AML) cells and an orthotopic mouse xenograft model we demonstrate that mutant TET2allele dosage significantly affects sensitivity to 5-azacitidine hypomethylating therapy in AML, with biallelic mutation conferring hypersensitivity relative to monoallelic mutation. In the presence of 5-azacitidine, cell clones with biallelic TET2mutation had significantly lower cloning efficiency (P= 3 x 10-3) and proliferation in liquid culture (P< 1 x 10-4) compared to isogenic clones with monoallelic TET2mutation. Mixed populations of monoallelic and biallelicTET2mutated HEL AML cells were transplanted via intrafemoral injection into Rag2−/−Il2rg−/−129×Balb/c mice, and treatment with 5-azacitidine resulted in significant negative in vivoselection against TET2null cells relative to cells with monoallelic TET2mutation (P= 4 x 10-4). Methylation analysis revealed the acquisition of an overall hypermethylation phenotype in TET2null cells and RNA sequencing identified significant down-regulation of ABCB1transcript, resulting in concomitant pronounced down-regulation of the MDR1 drug efflux transporter at the protein level. RNA sequencing pathway analysis also identified a global effect on ribosome pathway (KEGG pathway ko03010) transcript levels (Padjusted= 0.002), evidenced by down-regulation of numerous RNA polymerase II components in cells with bi-allelic TET2mutation compared to cells with monoallelic TET2mutation.

Published
2019
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