A7: Control of stem cell fate by key regulators of post-embryonic hematopoiesis

 

Christof von Kalle and Hanno Glimm

 

Common retroviral vector insertion sites (CIS) are highly overrepresented in clinical gene therapy studies, demonstrating that insertional activation of particular genes leads to a selective advantage in hematopoiesis. We hypothesize that CIS mark candidate regulatory genes of hematopoietic stem cells whose deregulation represents an early event in leukemogenesis. We aim to identify candidate stem cell regulatory genes by analyzing the complete integration site repertoire in a clinical gene therapy study. The impact of candidate genes on hematopoietic stem cell biology will be analyzed in vitro and in vivo. Genetic progression of clonal dominance into leukemia will be modeled by a secondary mutation screen.