Bone marrow stem cells have a unique ability to continue to divide throughout life. This “self-renewal” capability is critical for sustaining production of blood cells but also has important roles in leukemia. Leukemia cells often hijack these pathways to drive growth of the malignant cells. The programs that control stem cell self-renewal change during development from infancy to adulthood, which may contribute to the differences in pediatric and adult leukemia. The underlying mechanisms that determine these developmental changes are not known. Our recent work has identified a new gene, BCLAF1, that regulates stem cell self-renewal functions and may have a role in leukemia. Our goal is to understand how BCLAF1 regulates stem cell development and how these pathways are altered in leukemia. Our work will use mouse models to focus on:
· Characterizing the role of BCLAF1 in normal stem cell function throughout development.
· Determining the mechanism by which BCLAF1 regulates stem cell self-renewal.
· Determining the role of BCLAF1 in acute myelogenous leukemia (AML).
Potential impact on child health
We expect these studies will provide important insights into age-specific programs of normal stem cell development and will reveal new perspectives on how these developmental programs may determine the differences in pediatric versus adult leukemias.