British scientists have unveiled key genetic changes underlying the development of T-cell acute lymphoblastic leukaemia (T-ALL) in children.
Researchers at the Institute of Cancer Research, London, genetically analysed individual cancer cells from 19 patients with STIL-TAL1-positive T-ALL. This allowed the team to create phylogenetic trees to explore how cancer cells ‘evolve’ as they multiply.
Importantly, fusion of the STIL and TAL1 genes occurred early and was common to all cancer cells, suggesting it was a critical ‘founder event’.
They found deactivation of the PTEN gene - which is active in suppressing cancer - in many cells, affecting about 50% of patients. This occurred later suggesting this was a secondary event.
Researcher Dr Caroline Furness said: "We need to understand how cancers evolve and unpick which mutations are key to triggering cancer development - and which are important for driving its growth and spread.
“Our study uncovered these crucial mutations in a type of leukaemia that accounts for around a quarter of cases of T-cell leukaemia in children and young adults.
“This will help us to develop more effective treatments, especially in those children who relapse, and kinder treatments that won’t cause life-long side effects.”
Dr Alasdair Rankin, director of research at Bloodwise, which backed the study, said: “Survival rates for childhood leukaemia have improved significantly and eight in ten children will now survive in the long-term. Treatments are still highly toxic and can have devastating side effects and there is a need to improve survival further.
“Every child’s leukaemia is complex and genetically different, which can cause obstacles to the development of targeted treatments. Although this is early work, this study has identified common faults that play a role in driving the disease in the majority of children with this subtype of leukaemia, paving the way for future treatments.”
Source: Furness, Caroline L., et al. "The subclonal complexity of STIL-TAL1+ T-cell acute lymphoblastic leukaemia." Leukemia (2018): 1.
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