Juerg Schwaller is group leader at that Department of Biomedicine of the University Hospital Basel affiliated with the Children’s Hospital beider Basel (UKBB). Research of the “Childhood leukemia group” aims to better understand the molecular mechanisms underlying induction and maintenance of acute myeloid leukemia (AML) a human cancer characterized by accumulation of white blood cells that are blocked in differentiation with aberrant self-renewal capacity. AML is the consequence of a limited number of functionally cooperating genetic lesions involving transcriptional regulators (e.g. MLL) of cellular differentiation and signaling mediators controlling proliferation and cell survival. We have established a series of transgenic mice to study the impact of the cellular origin for the biology and clinic of AML. Conditional expression of the AML-associated MLL-AF9 fusion oncogene in different cells of the hematopoietic hierarchy revealed that induction in long-term hematopoietic stem cells (LT-HSC) can result in a particularly aggressive disease characterized by invasive behavior and expression of the transcription factors EVI1 and ERG. Comparing the gene expression signatures from diseased mice with AML patients suggested that high levels of EVI1 and ERG also characterizes patients with particular poor outcome. Current studies aim to better understand whether the differential vulnerability of LT-HSC is related to a particular cellular identity or state. The susceptibility for leukemic transformation seems also dependent on the nature of a driver oncogene, as the MLL-ENL fusion had a different preferred target cells within the hematopoietic hierarchy than MLL-AF9. More recently we started to model AML affecting the erythro-megakaryocytic lineage such as acute megakaryoblastic leukemia (AMKL) and acute erythroblastic leukemia (AEL) both rare diseases for which the pathogenesis is poorly understood, and specific therapies are lacking. In parallel to AML modeling, our group constantly characterizes novel small molecules for their anti-leukemic potential. Our group has close collaborations with scientists in Switzerland (Antoine Peters. FMI; Cesar Nombela-Arrieta, Zürich) and abroad (Thomas Mercher, Paris; Stefan Knapp, Frankfurt; Simon Mendez-Ferrer, Cambridge, UK).