Notch signaling as a novel target of AML/ETO (A03)

The alternative splice variant of t(8;21) AML-ETO9a (AE9a) induces leukemia in mouse models upon retroviral transduction. However, analyses of patient data revealed no prognostic impact of AE9a expression in t(8;21)-positive AML patients. In addition, a novel conditional AE9a mouse model does develop leukemia. This suggests the requirement of additional “hits” for AE9a-driven leukemia. To identify those, retroviral insertional mutagenesis as well as biological/biochemical and clinical validation will be performed. In parallel, we want to decipher the contribution of a dysregulated Notch signaling pathway to AML onset using small molecule compounds that specifically modulate Notch signaling activity.

DFG Programme Collaborative Research Centres

Subproject of SFB 1074:  Experimental Models and Clinical Translation in Leukemia

Applicant Institution Universität Ulm

Project Heads Professor Dr. Hartmut Geiger; Professor Dr. Franz Oswald