Project A5: Characterization of regulatory and target pathways of microRNAs downstream of the leukemogenetic Hoxa9/Meis1 axis
The focus of the project is to identify and characterize the pathways down-stream of Hoxa9 and Meis1, specifically those directly and indirectly affecting microRNAs (miRNAs). Based on results from the first funding period, it is planned to further investigate the role and regulation of miR-155 and miR-708 in Hoxa9/Meis1-driven AML. Given the relevance of both HOXA9 and MEIS1 expression to hu-man AML and the upregulation of both miR-155 and miR-708 in various AML subtypes, it will be studied how miR-155 and miR-708 influence the Hoxa9 leukemic program through the expression of their targets and downstream effectors. In addition, functional analyses will be extended to other differentially expressed miR-NAs downstream of Hoxa9/Meis1 and by analysis of the compartment enriched for leukemia-initiating cells at the transcriptional and proteomic level. Considering the disease-spanning relevance of Hoxa9 and Meis1, their role in ALL will be dissected by establishing a novel ALL mouse transplantation model based on the overex-pression of Hoxa9/Meis1 in lymphoid conditions. The overall goal of the proposal is to define the commonalties and differences of the Hoxa9/Meis1 pathways in acute leukemias and uncover novel therapeutic targets.
For a list of project-related publications, please go to this page