Group leader Dr. Marieke Essers (PhD)
Our work has recently demonstrated, that the cytokine IFN?, which is produced by virally infected immune cells to block the infection of more mature blood cells, is able to activate the entire HSC pool including dormant ones. One of the goals of our research is to investigate the mechanism of IFN? mediated activation of HSCs and the potential role of the surrounding bone marrow stem cell niche in this process. Furthermore, we are currently exploring feedback loops in response to other stress situations like bacterial infection and response to chemotherapy induced cytopenia.
Leukemias are initiated and maintained by leukemic stem cells (LSCs), which can transplant the disease and show unlimited self-renewal activity. Most importantly, LSCs appear to be resistant to conventional therapies including anti-proliferative chemotherapy. The mechanisms responsible for this resistance remain unclear, however, their often dormant status as well as their localization in protecting stem cell niches are likely critical components. In our group we address whether LSCs can be targeted by driving them out of dormancy and mobilize them out of their niche. Our finding that IFNa activates normal HSCs to self-renew by putatively altering their niche interactions may open new possibilities to combine this drug with tyrosine kinase inhibitors such as Imatinib/Gleevec. This class of targeted therapies can achieve long term remission by eliminating progenitor and mature leukemic cells (as with chemotherapy alone) but spare the LSCs (see figure) and thus do not lead to cure. We are currently, using mouse models for leukemia and by testing leukemic patient samples, exploring whether combination therapies with IFN? or other activators can be developed to also target LSCs and thus potentially cure the disease.