University of Leeds research published in Nature today reveals a previously overlooked type of circular DNA that may contribute to childhood leukemia relapse. The study, led by Dr. Joan Boyes from the Faculty of Biological Sciences, builds upon previous research linking leukemia to excised signal circles (ESCs) – circular forms of DNA that are typically produced as a by-product when the body creates antibody genes.
The new findings show that these DNA fragments can persist in cancer cells and may play a role in driving relapse in patients with B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Dr. Boyes explains, “It has been known for over 40 years that small circular chromosomes, known as ‘double minutes’, are present in many cancers in addition to normal chromosomes. A further type of circular DNA, known as ESCs, were thought to be lost soon after they form. But we discovered that ESCs replicate and persist, just like double minutes.”
Through tracking DNA patterns, the researchers found that cells with ESCs present divide more frequently and trigger mutations in cancer-causing genes, potentially contributing to worse cancer outcomes. “We found, remarkably, that there are much higher levels of ESCs at diagnosis in many of the childhood leukemia patients who are most likely to suffer relapse, compared to those who remain in remission,” Dr. Boyes says.
This discovery could provide an early warning system for patients at risk of relapse, allowing for earlier detection and treatment. Dr. Beki James, a Consultant Paediatric Haematologist at The Leeds Teaching Hospitals, emphasizes the importance of this research, stating, “B cell acute lymphoblastic leukemia (B-ALL) is the most common blood cancer in children and young people. Treatment has improved dramatically, but although most children can be cured, we still see children relapsing and children dying from B-ALL.”
The research was made possible by funding from various organizations, including The Little Princess Trust, who contributed over £250,000 to support the early and continued stages of Dr. Boyes’ research. Phil Brace, CEO of The Little Princess Trust, states, “Discoveries like this really underline the importance of funding innovative research. Knowing that our support has helped uncover the inner workings of childhood leukemia and potentially found a new way to predict relapse is very impactful and reinforces our commitment to funding research that changes lives.”