Optimisation of novel GATA2 inhibitors as targeted therapeutics for therapy-resistant acute myeloid leukaemia

Acute myeloid leukaemia (AML) is an aggressive blood cancer with poor survival rates, where fewer than 3 in 10 patients live five years beyond their diagnosis. Standard chemotherapy often fails because a small group of “leukaemia stem cells” (LSCs) survive treatment, propagating the disease. These LSCs are resistant to standard therapies, can hide in the bone marrow, and are the main reason AML frequently returns after initial therapy.

No current treatment is able to specifically target and eliminate these LSCs. Our research focuses on a protein called GATA2, which plays a critical role in helping LSCs survive and resist treatment. GATA2 is found at abnormally high levels in around 25% of AML patients. Excitingly, our team has discovered novel small-molecule chemicals that block GATA2, selectively killing AML cells while sparing normal healthy cells.

We now aim to refine and improve these molecules so that they become suitable for future testing as potential medicines in patients. We will optimise their design, confirm their effectiveness in AML samples, and explore their use in combination with standard chemotherapies. 

This project has the potential to deliver the first targeted treatment for resistant AML, offering hope of more effective and less toxic therapies for patients.