The cells in our blood have several critical functions, including oxygen transport, prevention of continuous bleeding when wounds occur and protection against invading pathogens such as bacteria and viruses. All these cells are derived from one particular cell type, the so-called hematopoietic stem cell that replenishes itself and that has the potential to generate all the various blood cell types. These processes are regulated through the activity of various proteins and requires a strict regulation of their function. Aberrations in these processes therefore often result in malignancies, such as leukemia. In this research proposal, we wish to study the function of a family of proteins that is important for normal blood cell development and that is also often implicated in leukemia. We will study their role during blood cell development in human, thereby generating results that have the potential for immediate clinical impact.