Acute lymphoid leukemia (ALL), an aggressive type of cancer more common in children, is caused by a mutation in a gene that produces a protein linked to immunity, according to a study released today by Portuguese and Brazilian researchers.
The discovery paves the way for the development of new treatments for the disease, mainly for recurrent patients or for those in which conventional treatment does not work.
The study, published in the journal Nature Communications, was carried out by researchers from the Centro Infantil Boldrini (Brazil) and the Instituto João Lobo Antunes de Medicina Molecular, in Portugal, thanks to a joint grant from the Foundation for Research Support of the State of São Paulo ( FAPESP) and the Portuguese Foundation for Science and Technology (FCT).
“Based on an animal model developed in Brazil, we observed that the continuous activation of the IL-7R protein function, even at physiological levels of its expression, triggers the exaggerated proliferation of leukocytes (white blood cells) of the lymphocyte family, giving rise to leukemia severe acute”, explained José Andrés Yunes, a researcher at the Centro Infantil Boldrini and one of the authors of the study.
“The finding is important because, with a greater understanding at the molecular level of the disease and its genetic causes, it is possible to propose new treatments, especially for cases of recurrence or in which conventional treatment does not work”, added the researcher, cited in a statement from FAPESP.
The research revealed that the mutation in the IL-7R-producing gene, in addition to triggering leukemia, also stimulates new mutations in other genes, such as PAX5 and KRAS, which make the disease progress.
Unlike other studies of genes related to the appearance and growth of tumors, the researchers developed a transgenic mouse model that mimicked the mutation in the IL-7R gene without altering its transcriptional control.
“With this we were able to maintain the IL-7R mutant protein, which will continue to be produced at the same lymphocyte maturation stages and with the same intensity. In this way, the effect of the mutation can be evaluated at normal physiological levels”, explained the specialist.
Acute lymphoid leukemia is an overgrowth of B cells, the progenitors of lymphocytes.
The investigators responsible for the discovery clarified that the IL-7R mutation is not enough to give rise to leukemia. There are other genes that are also involved in the disease.
Currently, conventional therapies, such as chemotherapy, are effective in up to 90% of cases, however, as they are difficult treatments, the average cure rate in Brazil is between 40% and 50% in children and between 30% and 40% in adults.
The statement from FAPESP also highlighted that in Portugal some drugs that inhibit the molecular effects of IL-7R were tested.
“Studies were carried out with panels of drugs that may, in the future, be tested on animals and then on humans until their effectiveness is proven. In any case, they are important findings, as they also allow us to propose the most suitable treatment for each patient based on the identification of these alterations”, he concluded.