Identifying cancer susceptibility genes in paediatric ALL

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Published: 23 Jan 2020
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Dr Ching-Hon Pui - St Jude's Children's Research Hospital, Memphis, USA

Dr Ching-Hon Pui speaks to ecancer at the 2020 ALL Assembly meeting in Frankfurt about the differences in treating adults and children with acute lymphoblastic leukaemia.

He points out that inherited cancer susceptibility gene is important for the pathogenesis and treatment of the disease, and for the patient's family.

Dr Pui explains that by studying germline polymorphisms, we can learn about the racial/ethnic differences seen in leukaemia, along with why patients develop either B-cell or T-cell ALL.

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


One main difference between children and adults with leukaemia is that many children inherit the cancer susceptibility gene which is very important for the pathogenesis and for the treatment of the patients and also important for the family. We know that there’s a peak age for acute lymphoblastic leukaemia in children, most children are diagnosed of leukaemia between 2-5 years of age. This is the very onset of ALL. In the past we did not know why, we had all kinds of theories – infectious disease theory or isolation theory – but we now know that mainly it’s due to the germline cancer susceptibility genes.

Also by studying the germline we also know why there are racial ethnic differences in the types of leukaemia and also we know why most patients develop B-cell ALL instead of T-cell ALL. We know a lot. They can all be explained by the germline polymorphisms.

Also we now know that it is very important to find out if the patient has inherited any cancer susceptibility gene. Our early study found that perhaps 4-5% of child ALL have cancer susceptibility genes but at the time we only studied 60 cancer susceptibility genes. But now we’ve expanded the candidate genes to 150 and now we’ve found that almost 9% of children have cancer susceptibility genes but I’m sure we’ll find even more.

To know the cancer susceptibility genes is very important because it affects how the patient responds to treatment and also tells us what kind of treatment we should avoid. Because when patients have cancer susceptibility genes they are also more likely to develop a second cancer. So we have to avoid radiation, we have to avoid carcinogenic agents. This is for patients so we need to know that so that we know how to properly treat the patients.

However, it is also very important to the family members. When a patient has cancer susceptibility genes this means some of the siblings or maybe even the parents have a cancer susceptibility gene. Perhaps the family wants us to screen it because they want to identify those with the cancer susceptibility genes so that we can monitor them for early detection of cancer. So now the children with leukaemia actually can save the family member. As a matter of fact, we have already screened almost 80 families who have a child with leukaemia and a cancer susceptibility gene. We found in one fourth of them actually we found that some other family member had cancer susceptibility genes.  For some of them we actually by screening and monitoring them identified early onset of cancer so that we can treat them earlier to improve the cure rate.

So this is very important. This is not only limited to children with leukaemia, actually patients with solid tumours and brain tumours, they probably have an even higher incidence of cancer susceptibility genes. So this is a new field but it’s a very important new field because it’s not only important for the patient himself or herself, it can also affect the family members.