Signaling in persisting leukemic stem cells in acute myeloid leukemia

• Applicant: Privatdozentin Dr. Cornelia Brendel
• Subject Area: Hematology, Oncology
• Term: from 2008 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 59021035

• Final Report Year: 2017

Final Report Abstract

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.

Publications

• (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
  (See online at 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
  (See online at 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
  (See online at 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
  (See online at 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
  (See online at 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
  (See online at 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
  (See online at 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
  (See online at 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.
  (See online at https://doi.org/10.1021/acsnano.6b06040)