Translational research

This research focus investigates the effects of the expression of genetic aberrations found in patients with acute leukaemia on normal blood development. To this end, the leukaemia-specific alterations are first cloned into expression vectors and expressed in normal murine or human blood cells. The effects of these leukaemia-specific changes on normal blood cells are investigated in suitable in vitro assays or in vivo in the murine transplantation model. The Institute is focussing in particular on the AML1-ETO fusion gene, the mutation of the NPM gene and the group of homeobox genes.

Another focus of the Institute is research into the significance of non-coding RNA molecules (RNAs that do not code for a protein) for normal haematopoiesis and for the development of leukaemia. The Institute has techniques for the exact quantification of the expression of microRNAs in different tissue cells and their stable expression in haematopoietic cells. Different models are used to investigate the differences in the expression of non-coding RNAs between healthy and leukaemic stem cells and which microRNAs act as oncogenes and which as tumour suppressor genes. Another focus is on the question of whether microRNAs could have therapeutic potential.

A key focus of the institute is the characterisation of leukaemic stem cells. The aim is to define differences between healthy and malignantly transformed stem cells that could be utilised for the development of selective therapeutic approaches. In a murine model, the working group was able to show that leukaemic stem cells of acute myeloid leukaemia express surface proteins that are not found on normal blood stem cells. We are currently investigating whether leukaemic stem cells also differ from normal blood stem cells in their surface profile in patients with acute myeloid leukaemia. This could provide a basis for the development of therapies that attack the leukaemic stem cell without impairing the function of the normal stem cell.

The understanding of normal haematopoiesis is the basis for our understanding of malignant transformed haematopoiesis. For this reason, several projects are looking at the question of which factors are crucial for the function of normal haematopoietic stem cells. The work focuses on the so-called homeobox genes, which play an essential role in normal haematopoiesis and, if their function is disrupted, can initiate leukaemogenesis.