Reduced_representation_OxBS_sequencing_of_mouse_haemopoietic_cells__KAMX__ASMX

Comprehensive analysis of AML genomes has revealed co-occurring mutations in DNA and histone modifying enzymes suggesting their crucial role in tumourigenesis. To gain inside into the role of those genes in AML we generated mouse models recapitulating human AML mutations in Kdm6a, Dnmt3a, Dnmt3aR882H, Idh1, Idh2, Smc3, Asxl1, Ezh2, Bcor. We hypothesise that aberrant chromatin and DNA modification and underlying effect on gene expression largely contribute to leukemogenesis. To test this hypothesis we propose to compare gene expression and DNA and histone modification in the presence or absence of single gene mutation in mouse hematopoietic stem and progenitor compartment in a pre-leukaemia setting. Characterisation of these models will inform the biology of AML, identify potential therapeutic targets and provide platforms for the assessment of novel therapeutics.