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
  (See online at https://doi.org/10.1007/s00108-010-2791-2)
• MicroRNA29a regulates the expression of the nuclear oncogene Ski. Blood 2011;118:1899–1902
  Teichler S, Illmer T, Roemhild J et al.
  (See online at https://doi.org/10.1182/blood-2010-09-306258)
• Oncogenic NRAS Primes Primary Acute Myeloid Leukemia Cells for Differentiation. PLOS ONE 2015
  Brendel C, Teichler S, Millahn A et al.
  (See online at https://doi.org/10.1371/journal.pone.0123181)
• Sorafenib induces paradoxical phosphorylation of the extracellular signal-regulated kinase pathway in acute myeloid leukemia cells lacking FLT3-ITD mutation. Leukemia & Lymphoma 2015
  Fouladi F, Jehn LB, Metzelder SK et al.
  (See online at https://doi.org/10.3109/10428194.2014.1003055)
• 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 J, Stolte M, Lohoff M et al.
  (See online at https://doi.org/10.1371/journal.pone.0150411)
• 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 E, Stabla K, Riera-Knorrenschild J et al.
  (See online at https://doi.org/10.1186/s12885-016-2589-2)