DKFZ Junior Group Mechanisms of Leukemogenesis

Cancer patients die from resistance to therapy and metastasis. These processes are based on genetic and epigenetic aberrations and require the support of the tumor microenvironment that supplies pro-survival and protective stimuli. Understanding the molecular mechanism of these processes will allow one to target aberrant (epi)genetic pathways, interrupt the support of the microenvironment and address resistance to therapy. The Cooperation Unit between the DKFZ and the University Hospital of Ulm is ideally suited to translate molecular findings on chronic leukemia towards clinical application with respect to prognostication and therapy.


FUTURE OUTLOOK

i) The identified epigenetic signatures are developed by the research network “PRECiSe” (coordinated by Daniel Mertens and Karsten Rippe) to stratify leukemia patients into different treatment groups.

ii) The aberrant epigenetic landscape drives transcription, and we used transcriptomic screens to identify compounds that target the microenvironmental support. We show that these repurposed substances are active in a leukemia mouse model via disruption of hypoxia-inducible pathways that are the most important support in the leukemic niche.