GRB10 IS A TUMOR SUPPRESSOR IN ACUTE MYELOID LEUKEMIA

Acute myeloid leukemia (AML) represents a major therapeutic challenge with high relapse rates due to the persistence of chemotherapy-resistant leukemic stem cells (LSCs). To eradicate AML, a better understanding of the mechanisms that regulate LSC survival and resistance is essential. The PI3K/mTOR signaling pathway controls key signaling factors that promote the expansion and survival of chemotherapy-resistant LSCs. The mTOR complex 1 is negatively regulated by the imprinted gene, growth factor receptor-bound protein-10 (Grb10). In human AML, low Grb10 levels correlates with adverse prognosis and increased relapse rate. To study the role of Grb10 in regulating AML in vivo, we developed a HoxA9-Meis1 and MLL-AF9 driven murine AML models with maternal deletion of Grb10 (Grb10m/+). Primary and secondary recipient mice transplanted with Grb10m/+ leukemia cells displayed decreased survival (p