Infections and the development of childhood leukaemia

14 September 2015

Dr Ian Hampson and Dr Lynne Hampson, University of Manchester

Exposure to infection has long being implicated as a cause of childhood leukaemia but no specific infection has ever been identified. Dr Hampson is using new and unique methodology to try to pinpoint the causal infection. This could have important implications for prevention as well as having diagnostic and prognostic value. 

Amount of grant: £190,204 | Date of award: May 2015 

Overview

The proposed work will make an important contribution by looking intensively and systematically for evidence of a role for infectious agents in ALL aetiology.
Positive results would have a significant impact on diagnostics in the short-term, and potentially lead to the development of novel therapies long-term.
External reviewer
Leukaemia is the most common form of childhood cancer, with up to 500 new cases every year in the UK. The survival rate is now approaching 90 per cent but the disease takes an enormous toll on young bodies, with one of the longest and most intensive treatment regimes of all childhood cancers.

The causes of childhood leukaemia are not well understood. In animals, the vast majority of leukaemias are caused by infection with specific types of virus. There is also a known virus that causes leukaemia in adult humans. But, despite indirect evidence that leukaemia in children may have an infectious cause, no specific infections have been identified.

Another theory of childhood leukaemia development – the ‘hygiene hypothesis’ - is that some infections acquired early in childhood might actually protect against leukaemia development.

A major problem with trying to identify the infection(s) that might be linked to childhood leukaemia development is that, with current technology, it is very hard to find any such infection without knowing what to look for. It is also not certain that any infection will still be present in the leukaemia cells.

The human immune system remembers infections that it has previously encountered with so-called ‘memory antibodies’. These can persist for many years after the infection, protecting against re-infection by the same virus.

With a previous grant from Children with Cancer UK, Dr Hampson and colleagues have developed and tested a unique method of profiling the antibodies contained in sets of pooled blood samples and comparing the different profiles.

They have developed methods that can use this information to predict the type and frequency of infections that have occurred in one population of children and not the other, without having any prior knowledge of which infections to look for.

They will use this approach to identify both past and current infections that are either unique or more common in children with acute lymphoblastic leukaemia (ALL) than in disease-free children and vice-versa using pooled blood samples from 100 children with ALL and 100 healthy children.

The most promising infections will be selected and further tests carried out to assess whether antibodies against these infections can be detected in individual blood samples taken from children with and without ALL.

They will then look at ways of detecting the infectious agent directly, rather than indirectly by testing for antibodies.

About the research team

The Hampson lab is well known for developing original and innovative techniques.
External reviewer
Dr Ian Hampson and Dr Lynne Hampson are specialists in understanding how tumour viruses cause cancer. Most notably, they were the first to discover that drugs normally used to treat HIV could eliminate human papilloma virus (HPV)- related to early stage cervical cancer.

Ian established the Viral Oncology Laboratories at St Mary’s Hospital, Manchester, in 1997 and now leads a group of 10 researchers, all engaged in research investigating the role played by a variety of viral infections as causes of human cancer. The group has proven expertise in the development of the kind of molecular technology needed for this work.

Our funding will continue to support the salary of Dr Tom Walker, who carried out the start-up project that laid the foundations for the current work.

What difference will this project make?

The fundamental questions being addressed in this research have the potential to make a major impact on our understanding of the causes of ALL and for the development of diagnostic/prognostic markers and therapeutics.
External reviewer
There is a substantial body of evidence pointing towards the involvement of an unidentified infectious agent in the development of ALL. This work should provide important new information about existence of such an agent. The impact of identifying a causal infection would be huge.

Identification of a causal infectious agent could potentially lead to either a vaccine, in the case of a viral infection, or antibiotic or antibacterial-based prevention in the case of a bacterial infection.

If the converse is demonstrated, that early acquisition of specific types of childhood infection protect against leukaemia, this could also inform a new means of prevention.

This work also has broad application for a range of other diseases.

Read more: Acute lymphoblastic leukaemia | Causes of childhood cancer

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