How can targeting HOXA9 transform AML treatment? Professor Brian Huntly, The University of Cambridge, is uncovering key genetic mechanisms to develop new, more effective treatments—offering hope for better survival and quality of life.

The challenge

Every year in the UK, over 3,100 people are diagnosed with Acute Myeloid Leukaemia (AML), an aggressive blood cancer with poor long-term survival rates. Despite improvements in understanding and treatments, AML remains a major unmet medical need, with a 5-year survival of only 22%. The disease is driven by various mutations, many of which converge on a particular protein, HOXA9. Higher than normal levels of HOXA9 are found in the leukaemic cells of about 70% of AML cases and are associated with worse outcomes.

However, while HOXA9 is central to AML development and progression, we know little about how it is regulated or how it controls other genes. Understanding these mechanisms is critical for developing new treatments to improve survival rates.

The science behind the research

This project focuses on uncovering how the protein HOXA9 operates in AML. Using cutting-edge tools developed in the lab, Professor Huntly and his team aims to:

1. Identify which genes HOXA9 directly regulates across different AML subtypes.
2. Investigate the precise mechanisms by which HOXA9 drives cancer growth.
3. Explore how HOXA9 itself is controlled at the genetic and protein levels, identifying potential weak points that could be targeted with new therapies.

The team will use novel tools and state-of-the-art techniques developed in their laboratory to determine how the levels of HOXA9 are controlled, which genes it regulates and how it may be targeted. The results of the experiments will also be validated using patient samples to ensure clinical relevance.

What difference could this research make?

This research aims to pinpoint new therapeutic strategies targeting the HOXA9 pathway, which could lead to more effective treatments for AML. By understanding how HOXA9 operates and is regulated, Dr Huntly hopes to identify vulnerabilities that can be exploited to halt AML progression.

This work could pave the way for therapies that improve survival rates and quality of life for AML patients. Additionally, it is hoped that insights from this study will have broader implications for understanding and treating other cancers driven by similar mechanisms. The ultimate goal is to turn AML from a life-threatening disease into one which is curable or at least which can be well-managed.

It is through innovative research like this that we can ultimately stop leukaemia devastating lives.