Delayed infection exposure as a trigger for childhood ALL

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Published: 24 Jun 2017
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Prof Julia Hauer - Clinic for Pediatric Oncology, Düsseldorf, Germany

Prof Hauer speaks with ecancer at EHA 2017 about results from a mouse model which suggests that infection in childhood following infant development in clean environments may increase the likelihood of developing paediatric leukaemia.

She considers how the timing of exposure to an immune challenge may act as this trigger, based on observations of a surge in cases as children entry pre-school, and what further experiments can be done to identify the exact mechanism or pathogen responsible.

Prof Hauer presented these results to the conference at a press session, here.

ecancer's filming has been kindly supported by Amgen through the ECMS Foundation. ecancer is editorially independent and there is no influence over content.

We are seeing in our hospital many children with acute lymphoblastic leukaemia and we have this striking age peak between two and six years where a lot of children develop acute lymphoblastic leukaemia. This is our interest, in fact, how does this age peak occur and one attractive hypothesis is can it be exposure to infection. What we know is at the age of two to six years many of these little children are exposed to infection for the first time when they enter the kindergarten, go to school, have contact with their socio-economic peer groups. So we think, yes, it can be and we now have for the first time very nice experimental evidence from our mouse models which we tried to recapulate the development of acute lymphoblastic leukaemia in childhood.

Which specific subset of leukaemia were you working with here?

We started this project with a very special and a very rare subset of acute lymphoblastic leukaemia in childhood which is this PAX5 loss of function background and then we were able to extend this hypothesis, so exposure to infection can trigger acute lymphoblastic leukaemia to the most commonest subtype, the ETV6-RUNX1 subtype of acute lymphoblastic leukaemia.

Are there any thoughts as to what specific infection it could be or is it just the immune challenge overall?
That’s a very good question and this is the subject of our further study. At the moment we do not know if it’s a specific pathogen, so specific bacteria, specific virus, or if it’s just regular stimulation of the immune system which is finally causing leukaemia. This needs to be figured out and then also to address therapeutic or preventive options for these children.

There was discussion during the press conference yesterday quoting the hygiene hypothesis, that children today are too clean, they don’t get ill early enough. Do you think that might be true?

It can be, so there are many epidemiologic data which support that, for example, in the socio-economic high standard countries where the children grow up in a very clean environment and go maybe to kindergarten very late, so at the age of two or three years, we see a higher incidence over the years in acute lymphoblastic leukaemia and this would give the hypothesis that in the poorer countries where the children are exposed very early from birth to many, many different pathogens and the immune system is challenged from birth on then this somehow protects from developing acute lymphoblastic leukaemia.

This was, of course, just working with the mouse model. Are there any plans to do retrospective analysis from populations to see if this does bear out in more human-centric settings?

Yes, it is. It will be very difficult to analyse it retrospectively and to analyse, for example, patient samples if they were exposed to infections at the time point they develop leukaemia. We will need more studies in experimental models to narrow down our hypothesis, to get a better impression of care. Is it bacterial, is it viral infection, and then go back to human cohorts to see if we can really recapulate this. But for the time being now the different hypotheses are still too broad to go back to human samples. This will take a while.