A groundbreaking study conducted by the University of Leeds has shed light on a previously overlooked factor that may contribute to childhood leukaemia relapse. The findings, published in Nature, suggest that a specific type of circular DNA may play a role in driving relapse in children with B-cell precursor acute lymphoblastic leukaemia (BCP-ALL).
The research builds upon previous studies that linked leukaemia to excised signal circles (ESCs) – circular forms of DNA that are typically produced as a by-product during the creation of antibody genes in the body. This new paper reveals that ESCs can persist in cancer cells and may trigger relapse in patients with BCP-ALL.
Lead author Dr Joan Boyes, from the University’s Faculty of Biological Sciences, explains, “For over 40 years, it has been known that small circular chromosomes, known as ‘double minutes’, are present in many cancers alongside normal chromosomes. However, we have discovered that ESCs not only replicate but also persist, similar to double minutes.”
Through tracking DNA patterns created when ESCs form, the researchers were able to show that cells with ESCs present have a higher rate of division compared to other cancer cells. These ESCs also trigger mutations in cancer-causing genes, potentially explaining why high levels of ESCs lead to worse cancer outcomes.
In their study, the team found significantly higher levels of ESCs in childhood leukaemia patients who are most likely to relapse, compared to those who remain in remission. This discovery could potentially serve as an early warning system for patients at risk of relapse, allowing for earlier intervention and better treatment outcomes.
Consultant Paediatric Haematologist at The Leeds Teaching Hospitals, Dr Beki James, comments, “B-cell acute lymphoblastic leukaemia (B-ALL) is the most common blood cancer in children and young people. While treatment has improved significantly, there are still cases of relapse and even death. This research helps us to better understand the behaviour of the leukaemia at a cellular level, providing important insights for developing tailored and effective treatments in the future.”
The Little Princess Trust, a charity dedicated to funding innovative research, contributed over £250,000 to support the early and continued stages of Dr Boyes’ research. CEO Phil Brace states, “Discoveries like this really underline the importance of funding innovative research. Knowing that our support has helped uncover the inner workings of childhood leukaemia and potentially found a new way to predict relapse is very impactful and reinforces our commitment to funding research that changes lives.”
Other supporters of the study include the Harley Staples Cancer Trust, Blood Cancer UK, and the Wellcome Trust. Dr Boyes expresses her gratitude towards these organizations, stating that without their support, none of this groundbreaking research would have been possible.
The research team hopes that these findings will lead to further advancements in identifying high-risk patients and developing more effective treatments for childhood leukaemia. With continued support and funding, they believe that they can make a significant impact in the fight against this devastating disease.
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