NCT Research

Clinical Cancer Research Program in AML/ALL

Expertise

Clinical activity of the AML/ALL Program focuses on allogeneic stem-cell transplantation and innovative trials (Schaich J Clin Oncol 2011& 2013; Serve J Clin Oncol 2013; Amadori J Clin Oncol 2013). The research program focuses on genomic instability and clonal evolution in complex karyotype AML and leukemia stem-cells (Bochtler J Clin Oncol 2013; Stein Nat Med 2010). The Krämer group develops small molecule inhibitors of IDH as a novel way of treating IDH-mutant AML. S. Fröhling uses RNA interference screens to identify critical and tractable effectors of MLL fusion genes and tyrosine kinase co-dependencies (Faber J Clin Invest 2013).

CCRP AML & ALL
 

Scientific Goals

  • Understanding genomic instability in clonal evolution and heterogenity in acute leukemias.
  • Development of small molecule inhibitors of mutant isocitrate dehydrogenase (IDH).
  • Identification of critical and pharmacologically tractable effectors of MLL fusion genes and the role of tyrosine kinase co-dependencies using large-scale RNA interference (RNAi).

  1. Bochtler T, Stölzel F, Heilig CE, Kunz C, Mohr B, Jauch A, Janssen JWG, Kramer M, Benner A, Bornhäuser M, Ho AD, Ehninger G, Schaich M, Krämer A: Clonal heterogeneity as detected by metaphase karyotyping is an indicator of poor prognosis in acute myeloid leukemia. J Clin Oncol 2013; 31:3898-3905.
  2. Bochtler T, Kirsch M, Maier B, Bachmann J, Klingmüller U, Anderhub S, Ho AD, Krämer A: Centrosomal targeting of tyrosine kinase activity does not enhance oncogenicity in chronic myeloproliferative disorders. Leukemia 2012; 26:728-735.
  3. Leber B, Maier B, Fuchs F, Chi J, Riffel P, Anderhub S, Wagner L, Ho AD, Salisbury JL, Boutros M, Krämer A: Proteins required for centrosome clustering in cancer cells. Science Translational Medicine 2010; 2:33ra38.
  4. Stein S, Ott MG, Schultze-Strasser S, Jauch A, Burwinkel B, Kinner A, Schmidt M, Krämer A, Schwäble J, Glimm H, Koehl U, Preiss C, Ball C, Martin H, Göhring G, Schwarzwaelder K, Hofmann W-K, Karakaya K, Tchatchou S, Yang R, Reinecke P, Kühlcke K, Schlegelberger B, Thrasher AJ, Hoelzer D, Seger R, von Kalle C, Grez M: Genomic instability and myelodysplasia with monosomy 7 consequent to EVI1 activation after gene therapy for chronic granulomatous disease. Nature Medicine 2010; 16:198-204.
  5. Faber K, Bullinger L, Ragu C, Garding A, Mertens D, Miller C, Martin D, Walcher D, Döhner K, Döhner H, Claus R, Plass C, Sykes SM, Lane SW, Scholl C,* Fröhling S*. CDX2-driven leukemogenesis involves KLF4 repression and deregulated PPAR signaling. J Clin Invest 2013; 123:299-314. *Equal contribution.