A synthetic lethal screen to identify novel targets for therapy in acute myeloid leukemia

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

• Final Report Year: 2017

Final Report Abstract

The data provide strong evidence that cancer cells survive ara-C induced DNA-damage by increasing translesional DNA-synthesis. Depletion of genes that code for important proteins responsible for translesional DNA-synthesis re-sensitizes cancer cells towards ara-C. The data generated within the KFO210 thus may result in novel therapeutic approaches by targeting these genes or involved processes in the future. A first step in this direction may be the combined usage of a Neddylation inhibitor targeting the cullin-RING family of E3 ligases together with ara-C. And indeed, recently first clinical data have shown a synergistic effect.

Publications

• Chronic myeloid leukemia. Diagnostics, therapy and future strategy. Internist (Berl) 2011;52(3):283–93
  Burchert, A. & Neubauer, A.
  
• MicroRNA29a regulates the expression of the nuclear oncogene Ski. Blood 2011;118:1899–1902
  Teichler, Sabine; Illmer, Thomas; Roemhild, Josephine; Ovcharenko, Dmitriy; Stiewe, Thorsten & Neubauer, Andreas
  
• Oncogenic NRAS Primes Primary Acute Myeloid Leukemia Cells for Differentiation. PLOS ONE 2015
  Brendel, Cornelia; Teichler, Sabine; Millahn, Axel; Stiewe, Thorsten; Krause, Michael; Stabla, Kathleen; Ross, Petra; Huynh, Minh; Illmer, Thomas; Mernberger, Marco; Barckhausen, Christina & Neubauer, Andreas
  
• Sorafenib induces paradoxical phosphorylation of the extracellular signal-regulated kinase pathway in acute myeloid leukemia cells lacking FLT3-ITD mutation. Leukemia & Lymphoma 2015
  Fouladi, Fariba; Jehn, Lutz B.; Metzelder, Stephan K.; Hub, Florian; Henkenius, Katharina; Burchert, Andreas; Brendel, Cornelia; Stiewe, Thorsten & Neubauer, Andreas
  
• A Gain-Of-Function Mutation in the Plcg2 Gene Protects Mice from Helicobacter felis-Induced Gastric MALT Lymphoma. PLOS ONE 2016;11(3): e0150411
  Gossmann, Jennifer; Stolte, Manfred; Lohoff, Michael; Yu, Philipp; Moll, Roland; Finkernagel, Florian; Garn, Holger; Brendel, Cornelia; Bittner, Alwina; Neubauer, Andreas & Huynh, Minh Q.
  
• A rational two-step approach to KRAS mutation testing in colorectal cancer using high resolution melting analysis and pyrosequencing. BMC Cancer 2016; 16:585
  Mack, Elisabeth; Stabla, Kathleen; Riera-Knorrenschild, Jorge; Moll, Roland; Neubauer, Andreas & Brendel, Cornelia