ALL is a very complex disorder and what is less known is how the events are accumulating in the blood or in the bone marrow. For understanding this there were studies that were either in the Guthrie cards, on the blood spots that are taken at diagnosis in the peripheral blood of children, which is the only source of neonatal DNA where you can look whether the fusion that has been detected at diagnosis of leukaemia can be back-tracked and detected to show whether it was already present at birth. This has been done in the past and we also contributed to this and demonstrated that the first event for leukaemia in most of the cases for acute lymphoblastic leukaemia is already there at birth. That doesn’t mean that it’s inherited by the parents, the parents are negative for the translocation that has been detected. So it occurs in utero during the pregnancy. Then this is not sufficient to get the leukaemia, that’s also important because only 1% of children with this fusion which is common in leukaemia, only 1% of them will get the leukaemia. So the approximate rate is 1% for having positivity and 1% of the 1% to get leukaemia.
Studies on twins were also very important to understand what is prenatal and what is postnatal. Because in the case of monozygotic monochorionic twins if one is diagnosed with leukaemia the chance that the other one could get leukaemia is about 10%. So in the unfortunate case that also the second one getting leukaemia they are called concordant twins with ALL and in the concordant twins you can check whether the lesions are exactly the same or they are different. What is identical is prenatal, what is different is postnatal and that was the assumption and what we found in the concordant twins.
Even more important is for discordant twins because of course for the parents in particular and having positivity for a lesion which is associated with leukaemia is a worry. But it’s only a matter of counselling for the possibility to get cancer, that doesn’t mean that those twins, those discordant twins, will get leukaemia in all the cases. So it’s very important to monitor the healthy twin and this has been done, not in our hands but by colleagues, and this demonstrated having the first fusion is not sufficient to get the leukaemia.
Important is also that there is nothing to do for preventing leukaemia. Unfortunately we don’t know what is causing leukaemia and this is a lack in information for the parents with discordant twins.
