Childhood leukemia can occur during fetal development
Sist anmeldt: 14.06.2024
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A team of researchers has demonstrated that some childhood leukemias begin during embryonic development, although they do not appear until several months after birth.
The team includes researchers from the Institute of Oncology of the University of Oviedo (IUOPA), the Josep Carreras Leukemia Research Institute, the University of Barcelona and the Center for Biomedical Research in Cancer (CIBERONC). The study was published in the journal Leukemia.
Acute myeloid leukemia is the second most common type of acute leukemia in children and can be diagnosed during the first months of life. The early onset of the disease led to suspicion that the tumor may be of prenatal origin. However, this theory has been difficult to prove due to the lack of prenatal or birth samples.
“The opportunity to study the origins of this leukemia arose from the case of a 5-month-old infant who was diagnosed with acute myeloid leukemia at the Niño Jesús Hospital in Madrid,” explains Pablo Menéndez, ICREA professor at the University of Barcelona and the Josep Carreras Institute. "Parents who saved blood from the umbilical cord opened up a line of research that was previously impossible."
Using precision medicine techniques, the researchers analyzed the entire genome of the tumor. Unlike adult tumors, where thousands of mutations are found, only two chromosomal abnormalities were identified in this leukemia.
“Genomic analysis allowed us to develop a personalized diagnostic method for monitoring the disease,” says José 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 tumor arose and in what order these mutations appeared," he adds.
These questions are difficult to answer because such tests require blood samples from the infant before diagnosis is made, which is not possible in the vast majority of cases. However, in this case, the existence of a frozen cord blood sample allowed the researchers to separate different populations of blood cells at birth and study whether any of the chromosomal abnormalities found in the tumor were already present during fetal development.
The study found that a translocation between chromosomes 7 and 12 was already present in some hematopoietic stem cells in umbilical cord blood. In contrast, another chromosomal abnormality, trisomy 19, was not present in the fetus but was found in all tumor cells, suggesting that it contributes to the increased malignancy of leukemia cells.
“These data are extremely important for understanding the development of this devastating disease, and the existence of this umbilical cord blood sample was decisive for carrying out research that has not been possible so far in acute myeloid leukemia,” adds Talia Velasco, a researcher at the Josep Carreras Institute and University of Barcelona, co-author of the study.
In addition to reconstructing the genomic changes that cells undergo to cause this leukemia, the study also identified a molecular mechanism that has not previously been observed in this type of leukemia that causes activation of the MNX1 gene, which is often altered in this type of tumor.
Knowledge of these changes is necessary for the development of cellular and animal models that will allow us to understand the evolution of the disease and develop new treatments for these pathologies.