PRECiSe – Pretherapeutic epigenetic CLL patient stratification
PRECiSe is a BMBF funded research project with the e:Bio program (module II) that takes a mechanistic approach to the identification of novel epigenetic biomarkers by understanding how BCR signaling in CLL patient cells impacts on the deregulated transcriptional and epigenetic landscape and the effectivity of new therapeutic inhibitors of BCR signaling depending on the patient-specific epigenetic landscape. It has been initiated based on the emerging paradigm shift in cancer therapy: Global DNA damaging chemotherapies are becoming replaced by personalized treatments with defined molecular therapeutic goals. This general development specifically applies to chronic lymphocytic leukemia (CLL) where novel therapies target microenvironmental interaction and B-cell receptor (BCR) signaling.
On this basis, we will further develop the application of epigenetic biomarkers for testing in clinical trials: (i) to overcome chemoresistant disease, where we aim to understand the molecular mode of action via its imprint on the epigenetic networks in CLL cells and (ii) where we will exploit the opportunity to identify epigenetic signatures that predict response to first-line treatment in asymptomatic patients.
Figure legend: Global loss of DNA methylation in CLL. Data analysis by Murat Iskaar