In spite of the possibility of a cure in a large number of cases, there are other childhood leukaemias which are still very difficult to cure and they continue to cause great suffering to patients and their families. There is a very rare type of acute lymphoblastic leukaemia (6-8 cases per year in Spain) which is diagnosed especially in breast-feeding babies and which is almost always fatal. This is infant t(4;11) (MLL-AF4+) pro B-cell acute lymphoblastic leukaemia. Dr. Pablo Menéndez, Scientific Director at the Josep Carreras Leukaemia Research Institute's University of Barcelona Hospital Clínic Campus and his team are concentrating their research on this kind of leukaemia.

It is true that t(4;11) (MLL-AF4+) pro B-cell acute lymphoblastic leukaemia can affect people of all ages, but it is especially common amongst babies less than 12 months of age. Dr. Pablo Menéndez says, "It is difficult to cure because there are still many questions without answers. For example, we do not know in which cell the MLL-AF4 alteration originates, in which cell MLL-AF4 becomes abnormal, why the latency is so short, what additional mutations cooperate with MLL-AF4 (the genome of these babies is surprisingly stable), the reason why a high percentage of these patients is resistant to glucocorticoids, something that does not happen in other acute childhood leukaemias, etc. To a large extent, all these lacunae in our knowledge are basically due to the fact that, after fifteen years working on the disease, we have not been able to reproduce this leukaemia in the laboratory. The animal models and cells generated do not 'reproduce' the disease".

Generally speaking, scientists need to generate a 'laboratory model' to reproduce the disease, whether that be an animal model or a cellular model, to study how and why the disease develops or, in other words, to understand the cellular and molecular mechanisms that produce the disease. Understanding the origin and evolution of the disease precedes discovery of possible new treatments. This is one of the challenges facing Dr. Menéndez and his team.

Dr. Menéndez goes on to say, "In the case of childhood cancers we can not ignore the fact that "something has gone wrong" during embryo to foetal development, in other words, during pregnancy. I do not define this leukaemia as a cancer, but as a "development disease". All cellular, molecular, genetic and epigenetic processes etc., are incredibly regulated, like a Swiss watch, during the nine months of pregnancy, from fertilisation to birth. It is easy to understand how a malfunction in that regulation can lead to illness. The rate of cell proliferation and differentiation (the two properties that are jointly altered in cancer) is much more active and decisive during the formation, from a zygote, of a baby than it is during the formation of an adult from a baby. That is why at every stage of development there are cancers associated with specific tissues and age ranges which affect tissues that are very active at any given time".

Dr. Pablo Menéndez and his team are also researching other kinds of childhood leukaemias such as, for example, B-acute lymphoblastic leukemia (B-ALL) with good prognosis hyperdiploidy, which is characterised by presenting 5 - 10 extra chromosomes. This leukaemia responds very well to chemotherapy and the team is investigating if its origin is due to a defect in the way cells segregate chromosomes.