New research from the laboratory of Professor Tracy Bryan, Head of the Cell Biology Unit at CMRI, has found for the first time that children with some forms of leukaemia have a high chance of carrying mutations in genes that impact chromosome ends – and that testing could prevent them experiencing toxic side-effects from their treatment.
Professor Bryan was contacted by two haematologists, Dr Alison Bertuch and Dr Monica Gramatages, at Texas Children’s Hospital in the US – because she is one of the world’s leading experts in telomerase.
Telomeres are the protective tips at the end of our DNA. When they are damaged and shortened, this can lead to cancer. Telomerase is a molecule in stem cells that normally protects telomeres from this shortening.
“They had sequenced the genomes of 94 children at their hospital who had presented with Acute Myeloid Leukemia (AML) or Myelodysplatic Syndrome (MDS), which are types of blood cancer, and had found a higher-than-expected number of mutations in one of the genes encoding telomerase,’’ Professor Bryan said.
“They needed to determine whether these new mutations impacted telomerase function, so turned to us due to our expertise in the techniques used to measure telomerase activity, many of which have been developed or refined in my lab.’’
Dr Christopher Tomlinson in Professor’s Bryan’s lab carried out all the laboratory experiments in the research.
“It has long been known that patients with inherited mutations leading to short telomeres (Telomere Biology Disorders) have a 200-fold greater risk than the general population of developing AML or MDS – this is because short telomeres can lead to genomic instability that triggers cancer,’’ Professor Bryan said.
“We found that paediatric AML/MDS patients were more likely than a control population to have mutations that affected telomerase function. Importantly, patients with TBDs have an exceptionally high risk of toxicity from cancer treatments, including the bone marrow transplant used to treat these leukemias, so picking up these children prior to treatment is very important for their clinical management.’’
Professor Bryan said it was the first time it was shown that these patients have a high chance of carrying a mutated gene which impacts telomere function.
“This has immediate implications for clinical practice, since it shows that clinicians need to be alert to subtle features of telomere-related disease in their leukemia patients – picking up that they have such a mutation would result in altered treatments that are much less likely to result in excessive toxicity during treatment.
These findings provide a strong case for the routine screening of children who present with AML or MDS for mutations that may impact telomere maintenance.’’
The paper titled, Clinical and functional characterization of telomerase variants in patients with peadiatric acute myeloid leukaemia/myelodysplastic syndrome
, was published in the journal Leukemia this week, and you can read the full article here