Student Projects

The role of the immune system in disease evolution and treatment response in AML

Project Supervisor/s

Can be adapted in scope for Honours, Masters or PhD project

Acute myeloid leukaemia (AML) is an aggressive blood cancer characterised by the excessive production of immature myeloid elements. AML is a genetically heterogeneous disease in that it is known to be driven by an extensive list of somatic mutations and chromosomal re-arrangements. We have demonstrated that the endogenous immune system is only capable of mounting a sufficiently powerful anti-AML immune response in specific molecular subtypes of AML. Through these studies we have demonstrated that mutations that drive the constitutive activation of Nras result in the upregulation of antigen presentation machinery and immunostimulatory ligands. Of great interest is that the overexpression of the oncogene Myc is sufficient to inhibit multiple aspects of this pro-immunogenic mutant Nras-driven phenotype. Futhermore, we have also demonstrated that treatment of AML with the commonly used therapy Azacitidine results in the upregulation of immunogenic ligands on the AML and changes in the composition of the immune microenvironment.

In this project we will use established models of mutant Nras-driven AML to determine how changes in Myc activity alter the expression of immunogenic ligands and if it also changes the composition of the immune microenvironment. We will also determine the dependency of Azacitidine treatment efficacy on the presence of a competent immune system, and how this relates to transcriptional and epigenetic changes that occur in the AML in response to treatment. These studies will primarily employ mouse procedural work, primary cell culture, flow cytometry and basic molecular biology. Mechanistic studies are likely to include the use of high content sequencing technologies like RNAseq, ATACseq and EMseq.

To apply for this project, please contact the project supervisor/s

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