In a groundbreaking discovery, UK researchers have identified new mechanisms that are instrumental in acute myeloid leukaemia, potentially opening the door to new strategies to combat the disease.
In a study performed by experts from the University of Sussex, researchers discovered that two major oncoproteins are potentially working together within leukaemia cells that affect both of their oncogenic signalling activity, which is their ability to modify genes and trigger tumour development. The scientists believe that the breakthrough may help design novel treatment strategies for fighting acute myeloid leukaemia.
The research findings are published in Haematologica.
Fresh insights into acute myeloid leukaemia
Acute myeloid leukaemia is an aggressive type of leukaemia that impacts leukocytes – a form of white blood cell that fights infections and prevents tissue damage. Each year in the UK, there are around 3,000 new cases of acute myeloid leukaemia; however, the disease usually has a poor prognosis and high relapse rates due to current chemotherapies being highly toxic and ineffective. The new oncoprotein discovery may provide hope for thousands of people living with the condition.
Dr Rhys Morgan, Lecturer in Biomedical Science at the University of Sussex, and Director of the Sussex Haematology Research Group said: “This is an important development because a better understanding of molecular interactions in cancer can open up new pathways for treatment and help us better understand how the disease progresses.
“We’ve known for a long time that each of these oncoproteins contributes to leukaemia progression but never fully understood how, which has hampered treatment design. This study has shown for the first time that these two ‘heavyweights’ in leukaemia physically interact and influence each other’s activity in acute myeloid leukaemia cells. The overactivity of a signalling molecule called beta-catenin is well established in the disease, but this oncogenic activity is dictated heavily by what other molecules it interacts with within a cancer cell.
“For the first time, we’ve been able to unravel beta-catenin’s interaction network in leukaemia cells and discovered that it interacts with another well-known signalling protein called Wilms Tumour 1 (WT1). WT1 is famously known to be mutated in a childhood kidney cancer called Wilms Tumours, but it’s also frequently overactive and mutated in acute myeloid leukaemia.”
Designing new treatments
Current treatment options for the disease that target beta-catenin have demonstrated limited success. Nevertheless, the researchers are confident that treatments that effectively disrupt its interaction with other proteins could help to combat the disease.
Dr Morgan concluded: “The next step for this research will be to try to understand exactly how the interaction of these two proteins contributes to leukaemia progression and then collaborate with structural biologists and medicinal chemists to strategise how this might be disrupted therapeutically.
“Estimates from our group at the University of Sussex, and others, suggest that between 40-80% of acute myeloid leukaemia cases exhibit some level of beta-catenin overactivity. So any therapy which can disrupt this leukaemia-promoting activity, has the potential to benefit a large number of patients with acute myeloid leukaemia – but also beyond.”
“This kind of research doesn’t happen without the kind donation of leukaemia or normal stem cells from patients and donors, so I’d like to extend my sincere thanks to all those who consent for their tissue to be used in medical research.”
