Junior Research Group Molecular Leukemogenesis

Dr. Stefan Gröschel

ChIP-seq and 4C-seq (middle panel) in myeloid blast cells (left panel) nominates a candidate EVI1 superenhancer, that can be targeted by CRISPR/Cas9. Deletion of the superenhancer leads to monocytic differentiation of blast cells.
© dkfz.de

Our scientific objectives are to understand pathways of gene regulation and to develop insights with innovate technologies to control gene expression in cancers driven by EVI1, most prominently acute myeloid leukemia. Together with collaboratives from our group and industry alliances we aim to translate these ideas as cancer therapeutic strategies.

Regulated expression of genes is orchestrated by surrounding control sequences, so-called „enhancers“. Enhancers can engage with target genes in different 3D nuclear chromatin interaction networks and function as cell type specific switches depending on tissue context, resulting in distinct gene expression programs that maintain cellular identity. This regulatory principle is exploited by oncogenes during tumorigenesis by 3D reorganization of enhancer-gene communications (enhancer hijacking). These physical interactions are either induced by gross chromosomal alterations (inversions, translocations, amplifications) or more subtle changes to the DNA code or even as aberrant dynamic chromatin changes without disruption of the linear DNA template.

Deregulation of the EVI1 oncogene is a key transforming event in the development of many malignancies and was initially discovered in high-risk leukemias, but remains largely unexplored in other entities, for example soft tissue sarcoma and other solid organ cancers. Both EVI1 function and the mechanism underlying its deregulation are poorly understood and the consequent lack of a targeted therapy against EVI1 creates a formidable clinical challenge. By applying functional genome diagnostics (next-generation sequencing-based, e.g. ChIP, targeted locus proteomics, 4C chromatin analysis) and genome editing (CRISPR technology) we aim to explore ways to reprogram the cancer cell's fundamental identity and revert the aggressive phenotype of these EVI1+ cancers. Toward these goals, we are also part of the ENHANCE consortium of the DKFZ, a highly interactive joint research collaboration of investigators from the DKFZ involved in basic and translational research with a focus on epigenetics.


Dr. Stefan Gröschel
Molecular Leukemogenesis (G240)
Deutsches Krebsforschungszentrum
Im Neuenheimer Feld 581
69120 Heidelberg
Tel: +49 6221 42 1613

Selected Publications

  • Gröschel S and Schlenk RF et al. (2013). Deregulated expression of EVI1 defines a poor prognostic subset of MLL-rearranged acute myeloid leukemias: a study of the German-Austrian Acute Myeloid Leukemia Study Group and the Dutch-Belgian-Swiss HOVON/SAKK Cooperative Group. J Clin Oncol. 31(1):95-103.
  • Gröschel S and Sanders MA et al. (2014). A single oncogenic enhancer rearrangement causes concomitant EVI1 and GATA2 deregulation in leukemia. Cell. 157(2):369-81.
  • Gröschel S and Sanders MA et al. (2015) Mutational spectrum of myeloid malignancies with inv(3)/t(3;3) reveals a predominant involvement of RAS/RTK signaling pathways. Blood. 125(1):133-9.
  • Avellino R et al. (2016). An autonomous CEBPA enhancer specific for myeloid-lineage priming and neutrophilic differentiation. Blood. 127(24):2991-3003.
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