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9 results on '"Opalka, Bertram"'

1. 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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3. 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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5. Dose‐dependent expression of GFI1 alters metabolism in the haematopoietic progenitors and MLL::AF9‐induced leukaemic cells.

Author

Patnana, Pradeep Kumar, Liu, Longlong, Frank, Daria, Nimmagadda, Subbaiah Chary, Behrens, Matthias, Ahmed, Helal, Xie, Xiaoqing, Liebmann, Marie, Wei, Lanying, Gerdemann, Andrea, Thivakaran, Aniththa, Humpf, Hans‐Ulrich, Klotz, Luisa, Dugas, Martin, Varghese, Julian, Trajkovic‐Arsic, Marija, Siveke, Jens T., Hanenberg, Helmut, Opalka, Bertram, and Dührsen, Ulrich

Subjects
ACUTE myeloid leukemia, OXIDATIVE phosphorylation, METABOLISM, GLUTAMINE, PROGENITOR cells
Abstract

Summary: Growth factor independence 1 (GFI1) is a transcriptional repressor protein that plays an essential role in the differentiation of myeloid and lymphoid progenitors. We and other groups have shown that GFI1 has a dose‐dependent role in the initiation, progression, and prognosis of acute myeloid leukaemia (AML) patients by inducing epigenetic changes. We now demonstrate a novel role for dose‐dependent GFI1 expression in regulating metabolism in haematopoietic progenitor and leukaemic cells. Using in‐vitro and ex‐vivo murine models of MLL::AF9‐induced human AML and extra‐cellular flux assays, we now demonstrate that a lower GFI1 expression enhances oxidative phosphorylation rate via upregulation of the FOXO1‐ MYC axis. Our findings underscore the significance of therapeutic exploitation in GFI1‐low‐expressing leukaemia cells by targeting oxidative phosphorylation and glutamine metabolism. [ABSTRACT FROM AUTHOR]

Published
2023
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6. Presence of the GFI1-36N single nucleotide polymorphism enhances the response of MLL-AF9 leukemic cells to CDK4/6 inhibition

Author

Vorwerk, Jan, primary, Sun, Kaiyan, additional, Frank, Daria, additional, Neumann, Felix, additional, Hüve, Jana, additional, Budde, Paulina Marie, additional, Liu, Longlong, additional, Xie, Xiaoqing, additional, Patnana, Pradeep Kumar, additional, Ahmed, Helal Mohammed Mohammed, additional, Opalka, Bertram, additional, Lenz, Georg, additional, Jayavelu, Ashok Kumar, additional, and Khandanpour, Cyrus, additional

Published
2022
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7. High Metabolic Dependence on Oxidative Phosphorylation Drives Sensitivity to Metformin Treatment in MLL/AF9 Acute Myeloid Leukemia

Author

Liu, Longlong, Patnana, Pradeep Kumar, Xie, Xiaoqing, Frank, Daria, Nimmagadda, Subbaiah Chary, Rosemann, Annegret, Liebmann, Marie, Klotz, Luisa Hildegard, Opalka, Bertram, Khandanpour, Cyrus, and Universitäts- und Landesbibliothek Münster

Subjects
hemic and lymphatic diseases, 610 Medicine and health, Medicine and health, heterogeneity, OXPHOS, MLL/AF9, metformin, Medizin, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, ddc:610, neoplasms, RC254-282
Abstract

Acute myeloid leukemia is a group of metabolic heterogeneous cancers, of which the long-term overall survival is still poor, especially in elderly patients. Targeting metabolic reprogramming in leukemic cells is becoming a promising strategy. The aim of our research was to explore the relation of genetic mutations with the metabolic phenotype and potential therapeutics to target metabolic pathway dependence. We confirmed the metabolic heterogeneity in AML cell lines and found the high dependence on oxidative phosphorylation in MLL/AF9 AML cells. Metformin could significantly repress the proliferation of MLL/AF9 AML cells by inhibiting oxidative phosphorylation., Acute myeloid leukemia (AML) is a group of hematological cancers with metabolic heterogeneity. Oxidative phosphorylation (OXPHOS) has been reported to play an important role in the function of leukemic stem cells and chemotherapy-resistant cells and are associated with inferior prognosis in AML patients. However, the relationship between metabolic phenotype and genetic mutations are yet to be explored. In the present study, we demonstrate that AML cell lines have high metabolic heterogeneity, and AML cells with MLL/AF9 have upregulated mitochondrial activity and mainly depend on OXPHOS for energy production. Furthermore, we show that metformin repressed the proliferation of MLL/AF9 AML cells by inhibiting mitochondrial respiration. Together, this study demonstrates that AML cells with an MLL/AF9 genotype have a high dependency on OXPHOS and could be therapeutically targeted by metformin., Finanziert durch den Open-Access-Publikationsfonds der Westf��lischen Wilhelms-Universit��t M��nster (WWU M��nster).

Published
2022
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9. Dexamethasone‐mediated inhibition of Notch signalling blocks the interaction of leukaemia and mesenchymal stromal cells.

Author

Ahmed, Helal Mohammed Mohammed, Nimmagadda, Subbaiah Chary, Al‐Matary, Yahya S., Fiori, Maren, May, Tobias, Frank, Daria, Patnana, Pradeep Kumar, Récher, Christian, Schliemann, Christoph, Mikesch, Jan‐Henrik, Koenig, Thorsten, Rosenbauer, Frank, Hartmann, Wolfgang, Tuckermann, Jan, Dührsen, Ulrich, Lanying, Wei, Dugas, Martin, Opalka, Bertram, Lenz, Georg, and Khandanpour, Cyrus

Subjects
MESENCHYMAL stem cells, STROMAL cells, DEXAMETHASONE, ACUTE myeloid leukemia, LEUKEMIA
Abstract

Summary: Acute myeloid leukaemia (AML) is a haematological malignancy characterized by a poor prognosis. Bone marrow mesenchymal stromal cells (BM MSCs) support leukaemic cells in preventing chemotherapy‐induced apoptosis. This encouraged us to investigate leukaemia‐BM niche‐associated signalling and to identify signalling cascades supporting the interaction of leukaemic cells and BM MSC. Our study demonstrated functional differences between MSCs originating from leukaemic (AML MSCs) and healthy donors (HD MSCs). The direct interaction of leukaemic and AML MSCs was indispensable in influencing AML cell proliferation. We further identified an important role for Notch expression and its activation in AML MSCs contributing to the enhanced proliferation of AML cells. Supporting this observation, overexpression of the intracellular Notch domain (Notch ICN) in AML MSCs enhanced AML cells' proliferation. From a therapeutic point of view, dexamethasone treatment impeded Notch signalling in AML MSCs resulting in reduced AML cell proliferation. Concurrent with our data, Notch inhibitors had only a marginal effect on leukaemic cells alone but strongly influenced Notch signalling in AML MSCs and abrogated their cytoprotective function on AML cells. In vivo, dexamethasone treatment impeded Notch signalling in AML MSCs leading to a reduced number of AML MSCs and improved survival of leukaemic mice. In summary, targeting the interaction of leukaemic cells and AML MSCs using dexamethasone or Notch inhibitors might further improve treatment outcomes in AML patients. [ABSTRACT FROM AUTHOR]

Published
2022
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