Acute myeloid leukaemia is the second most prevalent type of acute leukaemia in childhood, and it can be detected within a few months of life.

The disease's early beginning raised the possibility that the cancer originated before birth. However, validating this notion has been difficult due to the scarcity of prenatal or newborn samples.

The opportunity to study the origin of this leukaemia arose from the case of a five-month-old baby diagnosed with acute myeloid leukaemia at the Hospital Nino Jesus in Madrid,' explained Pablo Menendez, ICREA professor at the University of Barcelona and the Josep Carreras Institute.

'The parents, who had preserved the umbilical cord blood, opened a line of research that until now had not been possible to address,' added the researcher.

Using precision medicine techniques, researchers analysed the complete genome of the tumour. Unlike tumours in adults, where thousands of mutations are detected, only two chromosomal alterations were identified in this leukaemia.

'Genome analysis allowed us to design a personalised diagnostic method to monitor the disease,' says Xose S. Puente, Professor of Biochemistry at the University of Barcelona.

Puente, Professor of Biochemistry and Molecular Biology at the University of Oviedo. 'But these data raise new questions, such as when the tumour arose and in what order these mutations have appeared,' he highlights.

These questions are difficult to answer, since such research requires blood samples from the baby before the diagnosis, something that is impossible in the vast majority of cases.

However, in this particular case, a frozen umbilical cord sample allowed researchers to separate different populations of blood cells at birth and to study whether any chromosomal alterations detected in the tumour were already present during foetal development.

The study revealed a translocation between chromosomes 7 and 12 was already present in some haematopoietic stem cells in the umbilical cord.

In contrast, the other chromosomal alteration, a trisomy of chromosome 19, was not present in the foetus but was found in all tumour cells, suggesting that it contributes to increasing the malignancy of the leukemic cells.

'These data are highly relevant for understanding the development of a devastating disease, and the existence of this umbilical cord sample was crucial to be able for conducting a study that had been impossible until now in acute myeloid leukaemia', adds Talia Velasco, a researcher at the Josep Carreras Institute and the University of Barcelona and co-leader of the study.

In addition to reconstructing the genomic alterations that the cells undergo to generate this leukaemia, the study has also identified a molecular mechanism that had not been observed before in this type of leukaemia and which causes the activation of a gene, called MNX1, which is frequently altered in this type of tumour.

Knowledge of these alterations is essential for developing cell and experimental models that allow us to understand the disease's evolution and develop new therapies for treating these pathologies.

The study has been led by Xose S. Puente, Professor of Biochemistry and Molecular Biology at the University of Oviedo-IUOPA, Talia Velasco and Pablo Menendez, from the Josep Carreras Institute and the University of Barcelona, with participation from researchers from four other institutions, including the Hospital Infantil Universitario Nino Jesus, the Hospital Universitario Central de Asturias, the Instituto de Biomedicina y Biotecnologia de Cantabria and the Instituto de Investigacion Sanitaria La Princesa de Madrid.

This research has been made possible thanks to the collaboration of the parents and the Ministry of Science, Innovation and Universities, the European Research Council, the AECC Scientific Foundation, the Foundation Unoentrecienmil, the "La Caixa" Foundation, the Government of Catalonia, CIBERONC and the III Health Institute.