Scientists identify key genetic events responsible for initiating childhood leukemia
The key genetic events responsible for initiating the early stages of a type of childhood leukemia have been identified by scientists at The Institute of Cancer Research, London. Insights into the ‘founder’ genetic mutation for this type of leukemia, present in all the cancer cells, could be used in the development of new targeted drugs. The research, which was funded by the blood cancer research charity Bloodwise, is published in the journal Leukemia.
Leukemia develops when DNA faults – or ‘mutations’ – occur in maturing blood cells, triggering further genetic mutations that cause the cells to grow out of control.
Genetic faults in childhood leukemia cells evolve in a ‘Darwinian’ fashion – mutations that make certain cancer cells most resistant to treatment or multiply quickest are more likely to survive and drive the cancer forward. Cancer cells are constantly evolving genetically, explaining why cancer can sometimes return in a more aggressive form after treatment.
The Institute of Cancer Research (ICR) team used DNA analysis techniques to examine individual leukemia cells from 19 different children and young adults with STIL-TAL1-positive T-cell acute lymphoblastic leukemia (T- ALL), in order to determine the sequence in which these faults develop.
The researchers found that certain genetic alterations – the gene fusion STIL-TAL1, as well as inactivation of the CDKN2A gene - occurred very early in leukemia development.
The fusion between the STIL and TAL1 genes was likely to be a 'founder event' for this type of leukemia, present in all the cancer cells, meaning that targeting signalling pathways that are affected by this gene fusion could offer an effective way to treat the disease.
The PTEN gene, which is known to play an active role in suppressing cancer, was also deactivated in many individual leukemia cells. Half of the patients examined had errors affecting the PTEN gene in their cancer cells. This suggests that, while they occur later than the STIL-TAL1 gene fusion, PTEN gene alterations are key to maintaining leukemia growth and survival.
Dr Caroline Furness, who undertook the research in the laboratory of Prof Mel Greaves at The Institute of Cancer Research, London, said:
Dr Alasdair Rankin, Director of Research at Bloodwise, said:
T-ALL makes up around one in five cases of leukemia in children and young adults.
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