The role of the Ahi-1 oncogene in the regulation of hematopoietic stem cell development, function, and leukemogenesis

Chronic myelogenous leukemia (CML) is a cancer of the white blood cells. The disease starts when genetic changes in blood stem cells (hematopoietic stem cells, or HSCs) cause them to become malignant (leukemic stem cells) and grow uncontrollably. Normally, HSCs make all the white and red blood cells that function to protect our bodies from infections and to carry oxygen and nutrients to other cells in the body. In CML, leukemic stem cells crowd out all other cells in the bone marrow, leading to illness and eventually, if uncontrolled, death in the patient.

Dr. Kevin Lin's research group recently discovered that the Ahi-1 gene plays an important role in CML. The gene contributes to leukemic stem cell activity and can influence how these cells become resistant to current drug therapy. The goal of Dr. Lin’s research is to understand exactly how Ahi-1 contributes to CML disease development in HSCs and leukemic stem cells. Using a new mouse model that is deficient in this gene, he will examine what happens to the development and function of HSCs when Ahi-1 is absent. The findings from this project will contribute to our understanding of the biology of normal hematopoietic stem cells and malignant leukemia stem cells. This new knowledge will then be applied to develop better diagnostics and eventually better treatments for patients suffering from CML.