Characterization of regulatory and target pathways of microRNAs downstream of the leukemogeneic Hoxa9/Meis1 axis (A05)

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Based on our results from the first funding period, we will investigate the role, regulation and downstream targets of miR-155 and miR-708 in Hoxa9/Meis1-driven acute myeloid leukemia (AML). In addition, we will extend our analysis to the Leukemia-Initiating Cell (LIC) enriched compartment of Hoxa9/Meis1 cells at the transcriptional and proteomic level. Finally, considering the clinically relevant but not fully understood relevance of Hoxa9 and Meis1 in acute lymphoblastic leukemia (ALL), we will dissect their role in ALL through establishing a novel ALL mouse transplantation model based on the overexpression of Hoxa9/Meis1 in lymphoid conditions. Overall goal of our proposal is to define Hoxa9/Meis1 associated pathways in acute leukemias and uncover novel therapeutic targets.