Tumors, from prenatal mutation acute lymphoblastic leukemia in the first year of life

It affects children in the first year of life. It is a particular form of acute lymphoblastic leukemia and, in several cases, is related to the alteration of a gene called Nutm1. The alteration of this gene occurs when the chromosome in which it is located breaks and reconstitutes itself in a modified form, which characterizes, in several patients, the cells of this particular type of leukemia. In other words, it is a mutation that occurs before birth, and it is not something hereditary, because mom and dad are not carriers. The first to demonstrate this origin in the world were Italian researchers from the Tettamanti Foundation of the IRCCS San Gerardo dei Tintori in Monza.

The discovery, published in the ‘British Journal of Haematology’, was possible thanks to the analysis of the umbilical cord cells of a small patient who is now well, after having developed the disease several years ago. The umbilical cord had been preserved and donated to scientific research by the child’s family. The Nutm1 mutation is somatic, it is observed only in the leukemic cells of patients and not of parents and for this reason it is a non-hereditary alteration. The study was supported by the Tettamanti Foundation, the Maria Letizia Verga Committee (Genetic Passport project) and the Airc Foundation for Cancer Research.

“The work conducted jointly by our researchers Michela Bardini and Grazia Fazio is a further step forward in understanding the genetic components of this disease”, observed Giovanni Cazzaniga, head of the Leukemia Genetics Research Unit at the Tettamanti Foundation of San Gerardo. “The mutation of the Nutm1 gene is one of the dozens of genetic alterations linked to the onset of acute lymphoblastic leukemia and is observed, in particular, in approximately 5% of children affected in the first year of age. The alteration of Nutm1 is associated with a more favorable prognosis of the disease, as has been observed in recent international research, to which our group has also contributed. Therefore, studying and detecting this mutation, together with the other genetic alterations that characterize this pathology, should allow us to define even more precise and targeted therapeutic approaches in the future”.

Acute lymphoblastic leukemia is a blood cancer that originates from a particular type of white blood cells, called lymphocytes. It is called acute because it is generally aggressive and rapidly progressing. The form that manifests itself in the first year of life is observed in less than 5% of patients who develop this pathology each year. In Italy, there are approximately 35-40 new cases per million children and teenagers (source Aiom-Airtum).

The genetic alterations associated with acute lymphoblastic leukemia, including the one in the Nutm1 gene studied, are called chromosomal translocations: in practice, a break in the structure of a chromosome causes a part of it to move to another position on the same chromosome or sometimes even to another chromosome. Generally, mammalian cells, including human cells, are able to repair the lesion, restoring the original structure. In some cases, however, the exchange of fragments between non-homologous chromosomes persists, with the possibility of various pathologies arising, including tumors.

A specific area of ​​research at the Tettamanti Foundation focuses on genetic mutations associated with acute lymphoblastic leukemia. Thanks to the results of a previous study, researchers had observed that the prognosis of the disease diagnosed in the first year of age is better in patients in whom the Nutm1 gene is altered, while it is worse if another gene called Pax5 is involved. The results were published in 2020 in the journal ‘Blood’ and researchers from the University of Milan Bicocca and other Italian clinical centers collaborated on the Tettamanti Foundation study. The current results on the prenatal origin of the Nutm1 mutation, together with the 2020 discovery and the data collected in other ongoing studies in this area, go in the direction of increasingly targeted and precise therapies, experts highlight.