Grant: Operating Grant - PA: Cancer Research (bridge funding)

Acute myeloid leukemia (AML) is a type of white blood cell cancer that affects thousands of people in Canada alone. The treatment remains ineffective with about 50% patients dying per year. Thus, there is an urgent need to develop an effective cure for this devastating disease. Recently, our lab has found that miR-29a, a small RNA molecule, plays a key role in AML development. In humans, about 50% AML patients express a high level of miR-29a in their cancer cells. Our studies also reveal that this molecule regulates the function of the normal hematopoietic stem cell (HSC) (a small number of special subset of cells that function as the blood factory to produce all red and white blood cells), and that an increased expression of miR-29a makes a subset of white blood cell precursors becoming cancer stem cells. These findings thus suggest that the abnormal expression of miR-29a may convert normal blood cells into cancer stem cells, consequently developing into AML. In this proposal, we will test the hypothesis that miR-29a regulates the expression of genes that control HSC function and that a dysregulation of miR-29a expression may lead to development of AML. We will also identify which subset of originally normal white blood cells being converted into AML stem cells by miR-29a. Moreover, we will examine whether miR-29a also contributes to human AML development, progression, and survival. Completion of this work will elucidate the role and mechanisms by which miR-29a regulates blood cell generation and leukemia, and provide a biomarker for AML diagnosis and design of a personalized therapy. It may also provide a useful target to treat AML.