Leeds Teaching Hospitals NHS Trust (LTHT) has supported a University of Leeds-led study, which builds on earlier work that linked leukaemia, a type of blood cancer, to a type of circular DNA, called excised signal circles (ESCs), normally produced when the body creates antibody genes.
The new paper reveals for the first time ESCs can persist in cancer cells and may drive cancer returning in patients with the most common form of childhood leukaemia, B-cell precursor acute lymphoblastic leukaemia (B-ALL).
This breakthrough could help doctors spot which children are more at risk of relapse earlier than current methods allow, opening the door to more tailored and effective treatments in the future.
The study was co-authored by researchers at LTHT’s Haematological Malignancy Diagnostic Service (HMDS) at St James’s University Hospital, with funding from the Little Princess Trust.
The research also received additional support through the NIHR Leeds Biomedical Research Centre which is hosted at LTHT in partnership with the University of Leeds.
Dr Beki James, a Consultant Paediatric Haematologist at LTHT, said: “B cell acute lymphoblastic leukaemia 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.”
“This research takes us further forward in understanding how we can identify children at higher risk of relapse at diagnosis. It also enables us to better understand the behaviour of the leukaemia at a cell level. The more we understand the way it behaves, the more opportunity there is for us to develop tailored therapies in the future that are effective and potentially less toxic.”
Lead author Dr Joan Boyes from the University’s Faculty of Biological Sciences explained: “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.”
By tracking DNA patterns created when ESCs form, the researchers showed that the cells in which ESCs are present divide more frequently than other cells in the cancer. They also showed that ESCs trigger mutations in cancer-causing genes, which can help to explain why high ESC levels lead to worse cancer outcomes.
“We found, remarkably, that there are much higher levels of ESCs at diagnosis in many of the childhood leukaemia patients who are most likely to suffer relapse, compared to those who remain in remission,” said Dr Boyes.
“This discovery could provide an early warning system for those patients more likely to be at risk of relapse, potentially weeks earlier than current methods.
“Ultimately, this could help ensure that they are placed on the best treatments as soon as possible.”
Dr Boyes added: “We are extremely grateful to The Little Princess Trust, who funded this work from its earliest stages. Their continued funding enabled us to build on promising early experiments to expand the research further.
“Without their support, in addition to that of the Harley Staples Cancer Trust, Blood Cancer UK, and the Wellcome Trust, none of this work would have been possible.”
The Little Princess Trust contributed over £250,000 to support the early and continued stages of Dr Boyes’ research. Phil Brace, the CEO, said: “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.”
The study was funded with additional support by the Leeds Institute of Data Analytics, the Institute of Cancer Research, London, Newcastle University and VIVO Biobank.