Metabolic dependencies for improved therapeutic outcomes in chronic myeloid leukaemia

While the treatment of BCR-ABL1 driven chronic myeloid leukaemia (CML) with tyrosine kinase inhibitors (TKI) has been a success story of modern medicine, not all patients respond optimally, with a small but significant minority progressing to fatal blast crisis.

The inability of TKIs to eradicate leukaemic stem and progenitor cells (LSPC) provides a potential pool for subsequent relapse. This is exemplified by the dependence of most CML patients on lifelong TKI treatment, even in patients who achieve molecular responses.

hughes honours myeloid leukaemia

Universally, the presence of an activated tyrosine kinase drives metabolic changes, and the perturbation of these metabolic pathways provides potential avenues for exploration of therapeutic interventions. Targeting metabolic pathways may potentiate the effect of TKI therapies particularly in the LSPC compartment.

The aim of the project will be to investigate the metabolic pathways that exists within normal haematopoietic cells (important knowledge to avoid toxicity), and in LSPC including cases sensitive and resistant to TKIs to enable a clear understanding of whether the metabolome of LSPC can be targeted to sensitise this pool to TKI therapy.

This novel and innovative approach will likely provide a combinational treatment strategy with greater efficacy than current approaches, specifically in CML blast crisis.

Professor Tim Hughes

Supervisors

Professor Timothy Hughes

Co-supervisorsDr Ilaria Pagani

Research area: Cancer program - South Australian Health and Medical Research Institute

Recommended honours enrolment: Honours in Molecular and Biomedical Science

Tagged in Honours projects - Molecular and biomedical science, Honours projects - Molecular and biomedical science: Microbiology and immunology, Honours projects - Timothy Hughes, Honours projects - Ilaria Pagani