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14 results on '"Garz, Anne-Kathrin"'

1. The IMiD target CRBN determines HSP90 activity toward transmembrane proteins essential in multiple myeloma

Author

Heider, Michael, Eichner, Ruth, Stroh, Jacob, Morath, Volker, Kuisl, Anna, Zecha, Jana, Lawatscheck, Jannis, Baek, Kheewoong, Garz, Anne-Kathrin, Rudelius, Martina, Deuschle, Friedrich-Christian, Keller, Ulrich, Lemeer, Simone, Verbeek, Mareike, Götze, Katharina S., Skerra, Arne, Weber, Wolfgang A., Buchner, Johannes, Schulman, Brenda A., Kuster, Bernhard, Fernández-Sáiz, Vanesa, and Bassermann, Florian

Published
2021
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2. Direct modulation of the bone marrow mesenchymal stromal cell compartment by azacitidine enhances healthy hematopoiesis

Author

Wenk, Catharina, Garz, Anne-Kathrin, Grath, Sonja, Huberle, Christina, Witham, Denis, Weickert, Marie, Malinverni, Roberto, Niggemeyer, Julia, Kyncl, Michèle, Hecker, Judith, Pagel, Charlotta, Mulholland, Christopher B., Müller-Thomas, Catharina, Leonhardt, Heinrich, Bassermann, Florian, Oostendorp, Robert A.J., Metzeler, Klaus H., Buschbeck, Marcus, and Götze, Katharina S.

Published
2018
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3. The target landscape of clinical kinase drugs

Author

Klaeger, Susan, Heinzlmeir, Stephanie, Wilhelm, Mathias, Polzer, Harald, Vick, Binje, Koenig, Paul-Albert, Reinecke, Maria, Ruprecht, Benjamin, Petzoldt, Svenja, Meng, Chen, Zecha, Jana, Reiter, Katrin, Qiao, Huichao, Helm, Dominic, Koch, Heiner, Schoof, Melanie, Canevari, Giulia, Casale, Elena, Re Depaolini, Stefania, Feuchtinger, Annette, Wu, Zhixiang, Schmidt, Tobias, Rueckert, Lars, Becker, Wilhelm, Huenges, Jan, Garz, Anne-Kathrin, Gohlke, Bjoern-Oliver, Zolg, Daniel Paul, Kayser, Gian, Vooder, Tonu, Preissner, Robert, Hahne, Hannes, Tõnisson, Neeme, Kramer, Karl, Götze, Katharina, Bassermann, Florian, Schlegl, Judith, Ehrlich, Hans-Christian, Aiche, Stephan, Walch, Axel, Greif, Philipp A., Schneider, Sabine, Felder, Eduard Rudolf, Ruland, Juergen, Médard, Guillaume, Jeremias, Irmela, Spiekermann, Karsten, and Kuster, Bernhard

Published
2017

4. Immunomodulatory drugs disrupt the cereblon-CD147-MCT1 axis to exert antitumor activity and teratogenicity

Author

Eichner, Ruth, Heider, Michael, Fernandez-Saiz, Vanesa, van Bebber, Frauke, Garz, Anne-Kathrin, Lemeer, Simone, Rudelius, Martina, Targosz, Bianca-Sabrina, Jacobs, Laura, Knorn, Anna-Maria, Slawska, Jolanta, Platzbecker, Uwe, Germing, Ulrich, Langer, Christian, Knop, Stefan, Einsele, Herrmann, Peschel, Christian, Haass, Christian, Keller, Ulrich, Schmid, Bettina, Gotze, Katharina S., Kuster, Bernhard, and Bassermann, Florian

Subjects
Carcinogenesis -- Risk factors, Immunity -- Patient outcomes, Cellular proteins -- Health aspects, Biological sciences, Health
Abstract

Immunomodulatory drugs (IMiDs), such as thalidomide and its derivatives lenalidomide and pomalidomide, are key treatment modalities for hematologic malignancies, particularly multiple myeloma (MM) and del(5q) myelodysplastic syndrome (MDS). Cereblon (CRBN), a substrate receptor of the CRL4 ubiquitin ligase complex, is the primary target by which IMiDs mediate anticancer and teratogenic effects. Here we identify a ubiquitin-independent physiological chaperone-like function of CRBN that promotes maturation of the basigin (BSG; also known as CD147) and solute carrier family 16 member 1 (SLC16A1; also known as MCT1) proteins. This process allows for the formation and activation of the CD147-MCT1 transmembrane complex, which promotes various biological functions, including angiogenesis, proliferation, invasion and lactate export. We found that IMiDs outcompete CRBN for binding to CD147 and MCT1, leading to destabilization of the CD147-MCT1 complex. Accordingly, IMiD-sensitive MM cells lose CD147 and MCT1 expression after being exposed to IMiDs, whereas IMiD-resistant cells retain their expression. Furthermore, del(5q) MDS cells have elevated CD147 expression, which is attenuated after IMiD treatment. Finally, we show that BSG (CD147) knockdown phenocopies the teratogenic effects of thalidomide exposure in zebrafish. These findings provide a common mechanistic framework to explain both the teratogenic and pleiotropic antitumor effects of IMiDs., The drug thalidomide was originally prescribed as a sedative in the 1950s, and it became infamous for its devastating teratogenic effects (1). Due to their antiproliferative, anti-angiogenic and immunomodulatory properties, [...]

Published
2016
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5. The IMiD target CRBN determines HSP90 activity toward transmembrane proteins essential in multiple myeloma

Author

Sub Education Institute Chemistry, Biomolecular Mass Spectrometry and Proteomics, Heider, Michael, Eichner, Ruth, Stroh, Jacob, Morath, Volker, Kuisl, Anna, Zecha, Jana, Lawatscheck, Jannis, Baek, Kheewoong, Garz, Anne-Kathrin, Rudelius, Martina, Deuschle, Friedrich-Christian, Keller, Ulrich, Lemeer, Simone, Verbeek, Mareike, Götze, Katharina S, Skerra, Arne, Weber, Wolfgang A, Buchner, Johannes, Schulman, Brenda A, Kuster, Bernhard, Fernández-Sáiz, Vanesa, Bassermann, Florian, Sub Education Institute Chemistry, Biomolecular Mass Spectrometry and Proteomics, Heider, Michael, Eichner, Ruth, Stroh, Jacob, Morath, Volker, Kuisl, Anna, Zecha, Jana, Lawatscheck, Jannis, Baek, Kheewoong, Garz, Anne-Kathrin, Rudelius, Martina, Deuschle, Friedrich-Christian, Keller, Ulrich, Lemeer, Simone, Verbeek, Mareike, Götze, Katharina S, Skerra, Arne, Weber, Wolfgang A, Buchner, Johannes, Schulman, Brenda A, Kuster, Bernhard, Fernández-Sáiz, Vanesa, and Bassermann, Florian

Published
2021

6. The IMiD-Target Cereblon Determines Transmembrane Protein Quality Control Promoting Tumor Metabolism

Author

Heider, Michael, primary, Eichner, Ruth, primary, Stroh, Jacob, primary, Kuisl, Anna, primary, Zecha, Jana, primary, Lawatscheck, Jannis, primary, Rudelius, Martina, primary, Garz, Anne-Kathrin, primary, Lemeer, Simone, primary, Peschel, Christian, primary, Keller, Ulrich, primary, Götze, Katharina, primary, Buchner, Johannes, primary, Kuster, Bernhard, primary, Fernandez-Saiz, Vanesa, primary, and Bassermann, Florian, primary

Published
2019
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7. Die Kombination von Azacitidin und Crenolanib überwindet die Nischenprotektion und Expansion residualer leukämischer Stammzellen in der FLT3-ITD+ akuten myeloischen Leukämie mit wiederkehrenden Genmutationen in NPM1, DNMT3A und TET2

Author

Garz, Anne-Kathrin, Götze, Katharina S. (Prof. Dr.), and Küster, Bernhard (Prof. Dr.)

Subjects
fluids and secretions, Medizin und Gesundheit, hemic and lymphatic diseases, embryonic structures, hemic and immune systems, ddc:610, respiratory tract diseases
Abstract

Tyrosine kinase inhibitors (TKI) have limited impact as single agents in FLT3-ITD+ acute myeloid leukemia (AML), failing to eradicate leukemic stem cells (LSC) in the bone marrow. Using primary AML samples and a patient-derived xenograft model, we show that stromal resistance of FLT3-ITD+ LSC to TKI depends on co-existing epigenetic mutations. Combining the FLT3-selective TKI crenolanib with the hypomethylating agent azacitidine (AZA) abrogates stromal protection and survival of FLT3-ITD+ LSC. Tyrosinkinaseinhibitoren (TKI) zeigen limitierte Wirkung in der FLT3-ITD+ akuten myeloischen Leukämie (AML), da sie die leukämischen Stammzellen (LSZ) im Knochenmark nicht eliminieren. Unter Verwendung primärer AML Proben in vitro und xenotransplantierten Mäusen zeigen wir, dass zusätzliche epigenetische Mutationen die stromale Resistenz FLT3-ITD+ LSZ gegenüber TKI fördern. Die Kombination des FLT3-selektiven TKI Crenolanib mit dem hypomethylierenden Agens Azacitidin (AZA) überwindet die stromale Resistenz und eliminiert FLT3-ITD+ LSZ.

Published
2017

8. Azacitidine combined with crenolanib abrogates niche protection and expansion of residual leukemic stem cells (LSC) in FLT3-ITD+ acute myeloid leukemia (AML) with concurrent gene mutations in NPM1, DNMT3A or TET2

Author

Küster, Bernhard (Prof. Dr.), Götze, Katharina S. (Prof. Dr.), Garz, Anne-Kathrin, Küster, Bernhard (Prof. Dr.), Götze, Katharina S. (Prof. Dr.), and Garz, Anne-Kathrin

Abstract

Tyrosine kinase inhibitors (TKI) have limited impact as single agents in FLT3-ITD+ acute myeloid leukemia (AML), failing to eradicate leukemic stem cells (LSC) in the bone marrow. Using primary AML samples and a patient-derived xenograft model, we show that stromal resistance of FLT3-ITD+ LSC to TKI depends on co-existing epigenetic mutations. Combining the FLT3-selective TKI crenolanib with the hypomethylating agent azacitidine (AZA) abrogates stromal protection and survival of FLT3-ITD+ LSC., Tyrosinkinaseinhibitoren (TKI) zeigen limitierte Wirkung in der FLT3-ITD+ akuten myeloischen Leukämie (AML), da sie die leukämischen Stammzellen (LSZ) im Knochenmark nicht eliminieren. Unter Verwendung primärer AML Proben in vitro und xenotransplantierten Mäusen zeigen wir, dass zusätzliche epigenetische Mutationen die stromale Resistenz FLT3-ITD+ LSZ gegenüber TKI fördern. Die Kombination des FLT3-selektiven TKI Crenolanib mit dem hypomethylierenden Agens Azacitidin (AZA) überwindet die stromale Resistenz und eliminiert FLT3-ITD+ LSZ.

Published
2017

9. Azacitidine combined with crenolanib abrogates niche protection and expansion of residual leukemic stem cells (LSC) in FLT3-ITD+ acute myeloid leukemia (AML) with concurrent gene mutations in NPM1, DNMT3A or TET2

Author

Götze, Katharina S. (Prof. Dr.), Götze, Katharina S. (Prof. Dr.);Küster, Bernhard (Prof. Dr.), Garz, Anne-Kathrin, Götze, Katharina S. (Prof. Dr.), Götze, Katharina S. (Prof. Dr.);Küster, Bernhard (Prof. Dr.), and Garz, Anne-Kathrin

Abstract

Tyrosine kinase inhibitors (TKI) have limited impact as single agents in FLT3-ITD+ acute myeloid leukemia (AML), failing to eradicate leukemic stem cells (LSC) in the bone marrow. Using primary AML samples and a patient-derived xenograft model, we show that stromal resistance of FLT3-ITD+ LSC to TKI depends on co-existing epigenetic mutations. Combining the FLT3-selective TKI crenolanib with the hypomethylating agent azacitidine (AZA) abrogates stromal protection and survival of FLT3-ITD+ LSC., Tyrosinkinaseinhibitoren (TKI) zeigen limitierte Wirkung in der FLT3-ITD+ akuten myeloischen Leukämie (AML), da sie die leukämischen Stammzellen (LSZ) im Knochenmark nicht eliminieren. Unter Verwendung primärer AML Proben in vitro und xenotransplantierten Mäusen zeigen wir, dass zusätzliche epigenetische Mutationen die stromale Resistenz FLT3-ITD+ LSZ gegenüber TKI fördern. Die Kombination des FLT3-selektiven TKI Crenolanib mit dem hypomethylierenden Agens Azacitidin (AZA) überwindet die stromale Resistenz und eliminiert FLT3-ITD+ LSZ.

Published
2017

10. Polycomb protein RING1A limits hematopoietic differentiation in myelodysplastic syndromes

Author

Palau, Anna, primary, Garz, Anne-Kathrin, additional, Diesch, Jeannine, additional, Zwick, Anabel, additional, Malinverni, Roberto, additional, Valero, Vanesa, additional, Lappin, Katrina, additional, Casquero, Raquel, additional, Lennartsson, Andreas, additional, Zuber, Johannes, additional, Navarro, Tomàs, additional, Mills, Ken I., additional, Götze, Katharina S., additional, and Buschbeck, Marcus, additional

Published
2017
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11. Azacitidine combined with the selective FLT3 kinase inhibitor crenolanib disrupts stromal protection and inhibits expansion of residual leukemia-initiating cells in FLT3-ITD AML with concurrent epigenetic mutations

Author

Garz, Anne-Kathrin, primary, Wolf, Saskia, additional, Grath, Sonja, additional, Gaidzik, Verena, additional, Habringer, Stefan, additional, Vick, Binje, additional, Rudelius, Martina, additional, Ziegenhain, Christoph, additional, Herold, Sylvia, additional, Weickert, Marie-Theresa, additional, Smets, Martha, additional, Peschel, Christian, additional, Oostendorp, Robert A.J., additional, Bultmann, Sebastian, additional, Jeremias, Irmela, additional, Thiede, Christian, additional, Döhner, Konstanze, additional, Keller, Ulrich, additional, and Götze, Katharina S., additional

Published
2017
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13. Azacitidine in Combination with the Selective FLT3 Kinase Inhibitor Crenolanib Effectively Disrupts Stromal Protection of CD34+ Leukemia-Initiating Cells (LIC) in FLT3-ITD+ Acute Myeloid Leukemia (AML)

Author

Garz, Anne-Kathrin, primary, Habringer, Stefan, additional, Wolf, Saskia, additional, Vick, Binje, additional, Weickert, Marie-Theresa, additional, Jeremias, Irmela, additional, Spiekermann, Karsten, additional, Peschel, Christian, additional, Oostendorp, Robert A.J., additional, Keller, Ulrich, additional, and Götze, Katharina S., additional

Published
2015
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14. Azacitidine Directly Acts on the Mesenchymal Stromal Cell Compartment in Myelodysplastic Syndromes to Alter Niche Function and Suppress Malignant Hematopoeitic Stem/Progenitor Cells

Author

Wenk, Catharina, Garz, Anne-Kathrin, Huberle, Christina, Grath, Sonja, Witham, Denis, Weickert, Marie, Niggemeyer, Julia, Hecker, Judith, Kyncl, Michele, Müller-Thomas, Catharina, Mulholland, Christopher, Oostendorp, Robert A.J., Metzeler, Klaus H., Peschel, Christian, and Götze, Katharina S

Published
2017
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