Identification and characterization of prognostic signatures of therapy response in myeloid leukaemias

Leukaemia stem cells (LSC) need to be eradicated if we are to achieve a cure for myeloid leukaemias. Chronic myeloid leukaemia and acute myeloid leukaemia affect both adults and children, and both diseases have a heterogenous stem cell population that drive relapse and disease persistence and treatment resistance. We have identified transcriptional profiles in these diseases from patients that are good and poor responders to their treatments, that suggest common mechanisms that their LSC use to resist treatment.

Using an age and treatment agnostic approach, this project aims to interrogate single cell data to resolve the leukaemic stem heterogeneity and identify commonalities in these diseases that can be harnessed for patient stratification, biomarker development and drug vulnerabilities.

This project will use single cell transcriptomic data and multi-parametric flow cytometry to characterize leukaemia stem cells populations. Preclinical models, leukaemia stem cells assays, metabolic measurements and drug efficacy studies will be undertaken in this project to validate genes and/or pathways that can be of clinical benefit. Common features will be identified and gene profiles interrogated that are important for disease maintenance and persistence.

The project outcomes are expected to lead to biomarker and drug development that will has clinical significance.