Project Details
Projekt
Transcriptional and epigenetic mechanisms of Ski-driven leukemogenesis
Subject Area
Hematology, Oncology
Term
since 2014
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 259778674
Acute myeloid leukemia (AML) is a heterogeneous disease with a poor prognosis. Targeted therapies can only be applied to a fraction of AML-patients. Therefore, novel therapeutic approaches are urgendtly needed. We have previously identified SKI as being up-regulated in AML, especially in AML with monosomy 7, and showed that SKI acts as a repressor of retinoic acid induced myeloid differentiation. In the previous funding period we characterized epigenetic alterations caused by SKI overexpression in AML cell lines as well as AML patient cells using unbiased and genome-wide approaches. Our findings uncovered a dual function of SKI in gene regulation, as it contributes to gene activation as well as gene repression. Furthermore, our work identified promising novel epigenetic modifiers for therapeutic strategies of AML with upregulated SKI levels. In our renewal application we plan to address the following questions:1. How does SKI accomplish its dual and opposing gene-regulatory functions on the mechanistic level in AML cells?2. Does enhancer-bound SKI influence the generation of enhancer-derived transcripts (eRNAs) and long-range chromatin interactions in AML?3. Is disruption of c-MYB-dependent signaling beneficial for treatment of SKI-overexpressing AML?These data may ultimately result in novel treatment approaches in AML.
DFG Programme
Research Grants
