Signaling in persisting leukemic stem cells in acute myeloid leukemia

• Antragstellerin: Privatdozentin Dr. Cornelia Brendel
• Fachliche Zuordnung: Hämatologie, Onkologie
• Förderung: Förderung von 2008 bis 2015
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 59021035

• Erstellungsjahr: 2017

Zusammenfassung der Projektergebnisse

Taken together we have strong evidence that contact of leukemia cell to their stromal cell niche may influence their metabolic state by up-regulation of metabolic, predominantly glycolytic pathways and diminishment of intracellular ROS levels. ZnPP is a candidate molecule that specifically targets HL-60 cells which remain in closed contact to stromal cells. Our data obtained within the KFO210 funding period provide evidence for novel therapeutic approaches by targeting genes of the antioxidant pathway. Attachment of leukemia cells to stromal cells switches their metabolic state which seems to be essential for surviving the standard cytarabine chemotherapy therapy.

Projektbezogene Publikationen (Auswahl)

• (2011) Alpha4 integrin levels on mobilized peripheral blood stem cells predict rapidity of engraftment in patients receiving autologous stem cell transplantation. Blood 118(8): 2362-2365
  Hartz B, Volkmann T, Irle S, Loechelt C, Neubauer A, Brendel C
  (Siehe online unter https://doi.org/10.1182/blood-2011-02-331918)
• (2013) Good manufacturing practice-compliant animal-free expansion of human bone marrow derived mesenchymal stroma cells in a closed hollow-fiber-based bioreactor. Biochemical and Biophysical Research Communications 430: 325-330
  Nold P, Brendel C, Neubauer A, Bein G, Hackstein H
  (Siehe online unter https://doi.org/10.1016/j.bbrc.2012.11.001)
• (2014) Monitoring of acute myeloid leukemia patients after allogeneic stem cell transplantation employing semi-automated CD34+ donor cell chimerism analysis. Ann Hematol 93:279–285
  Hoffmann JC, Stabla K, Burchert A., Volkmann T., Bornhäuser M, Thiede C, Neubauer A, Brendel C
  (Siehe online unter https://doi.org/10.1007/s00277-013-1961-4)
• (2014) Oncogenic RAS primes primary acute myeloid leukemia blasts for differentiation. Plos One. 2015 Apr 22;10(4):e0123181
  Brendel C, Teichler S, Millahn A, Stiewe T, Krause M, Stabla K, Ross P, Illmer T, Mernberger M, Barckhausen C, Neubauer A
  (Siehe online unter https://doi.org/10.1371/journal.pone.0123181)
• (2015) Immunosuppressive capabilities of mesenchymal stromal cells are maintained under hypoxic growth conditions and after gamma irradiation. Cytotherapy 17(2):152-62
  Nold P, Hackstein H, Riedlinger T, Kasper C, Neumann A, Mernberger M, Fölsch C, Schmitt J, Fuchs-Winkelmann S, Barckhausen Ch, Killer M, Neubauer A and Brendel C
  (Siehe online unter https://doi.org/10.1016/j.jcyt.2014.10.004)
• (2016) A rational two-step approach to KRAS mutation testing in colorectal cancer using high resolution melting analysis and pyrosequencing. BMC Cancer Aug 2;16:585
  Mack E, Stabla K, Riera-Knorrenschild J, Moll R, Neubauer A, Brendel C
  (Siehe online unter https://doi.org/10.1186/s12885-016-2589-2)
• (2017) Immunosuppressive Capacity of Mesenchymal Stem Cells Correlates with Metabolic Activity and can be Enhanced by Valproic Acid. Stem Cell Research and Therapy 8:100
  Killer M, Nold P, Henkenius K, Fritz L, Riedlinger T, Barckhausen C, Frech, Hackstein H, Neubauer A, Brendel C
  (Siehe online unter https://doi.org/10.1186/s13287-017-0553-y)
• (2017) Optimizing conditions for labeling of mesenchymal stromal cells (MSCs) with gold nanoparticles: a prerequisite for in vivo tracking of MSCs. J Nanobiotechnology. 2017 Mar 29;15(1):24
  Nold P, Hartmann R, Feliu N, Kantner K, Gamal M, Pelaz B, Hühn J, Sun X, Jungebluth P, Del Pino P, Hackstein H, Macchiarini P, Parak WJ, Brendel C
  (Siehe online unter https://doi.org/10.1186/s12951-017-0258-5)
• (2017); Diverse Applications of Nanomedicine. ACS Nano Mar 28;11(3):2313-2381
  Pelaz B et al.
  (Siehe online unter https://doi.org/10.1021/acsnano.6b06040)