Targeting cancer stem cells as a new line of treatment for acute myeloid leukaemia
Background
Acute myeloid leukaemia (AML) is a highly aggressive blood cancer associated with poor survival rates. Despite advances in therapies for other types of leukaemia, progress in AML treatment remains limited. Chemotherapy continues to be the standard first-line approach, yet relapse is common. A key driver of treatment resistance is a rare population of cells known as leukaemic stem cells (LSCs). These cells can enter a dormant state, evade chemotherapy, and later reactivate to regenerate the disease. Their resilience and regenerative capacity make them a major barrier to cure. Innovative therapeutic strategies targeting LSCs are urgently needed to improve outcomes for patients with AML.
The research
Associate Professor Wang and her team have recently identified a specific type of protein, known as GPCR, that plays a critical role in the survival and self-renewal of LSCs. Notably, GPCR is uniquely expressed in LSCs and absent in normal human haematopoietic stem cells, making it a highly promising and selective target for novel AML therapies.
In this project, A/Prof Wang will investigate the molecular mechanisms that enable LSCs to persist and self-renew, with a particular focus on the role of the GPCR signalling pathway. By elucidating how this pathway contributes to LSC survival, her team aims to develop a targeted therapeutic strategy that inhibits GPCR activity. The effectiveness of this approach will be rigorously evaluated through pre-clinical models, laying the groundwork for a potential new treatment for AML.
The impact
By selectively targeting leukaemic stem cells, this novel therapeutic approach has the potential to eliminate AML at its source, preventing relapse and improving long-term survival. If pre-clinical studies demonstrate promising results, A/Prof Wang and her team aim to advance this strategy into clinical trials for patients with relapsed AML, offering new hope for those with limited treatment options.
Proudly supported by Box Rallies
This researcher was proudly funded through our partnership with Box Rallies (Shitbox Rally, Mystery Box Rally and Lunchbox Rally), an incredible organisation that has been raising funds for cancer research since 2009. To learn more or to take part in one of their unforgettable rallies, visit Box Rallies .
Project update
A/Prof Wang and her team have made a groundbreaking discovery of a novel chemo-resistant mechanism in leukaemic stem cells, regulated by the stress sensor protein GADD45A. This work was published in a globally recognised prestigious scientific journal (Loss of the stress sensor GADD45A promotes stem cell activity and ferroptosis resistance in LGR4/HOXA9-dependent AML – PMC).
Their findings reveal that targeting GADD45A, in combination with GPCR – a selective marker of leukaemic stem cells – could form the basis of a transformative therapeutic strategy. This dual-targeted approach holds promise for preventing relapse and significantly improving long-term survival in patients with AML.