A group of Spanish researchers from the Cancer Research Center (CIC), attached to the Higher Council for Scientific Research (CSIC), has completed a catalog of gene mutations present in peripheral T-cell lymphoma, a type of tumor that it affects the white blood cells, aggressive, with high mortality and for which there are no effective treatments.
The work, published in the EMBO Journal . has identified the different types of mutations that cause uncontrolled activation of the VAV1 gene, responsible for this highly virulent type of cancer.
Peripheral T-cell lymphomas develop from T lymphocytes, cells of the immune system whose function is to recognize and destroy those cells that have become dangerous , either because they have become cancer cells or because they have been infected. by a virus such as SARS-CoV-2.
However, when T lymphocytes undergo genetic alterations, they proliferate uncontrollably and these positive functions become harmful.
In this work, the researchers have shown that 51% of mutations that affect the VAV1 gene promote its uncontrolled activation and that these alterations are not all the same.
“There are five different types and, depending on the mutation that is present, different clinical characteristics develop both from the point of view of its malignancy and the therapeutic options”, explains Javier Robles Valero, author of the study together with Xosé R. Bustelo, both researchers from the CIC.
The most common functional subtype of VAV1 mutations in human tumors acts as a fully autonomous driver, that is, capable of inducing cancer when expressed in healthy T cells without the need for genetic alterations in other genes.
“This observation further underlines the fact that the presence of these mutations is not trivial, but that they are the main responsible for the origin of the tumor,” says Bustelo.
Until now, the relevance of the VAV1 gene mutations in the functional and clinical level was unknown, but thanks to this work “now we know which ones are important , what they do and how they influence the acquisition of the malignant properties of tumor cells”, adds the investigator.
In addition, the study has also developed an animal model that allows the generation of lymphomas in mice after the expression of VAV1 mutants in healthy T lymphocytes.
In any case, the main promise of this knowledge is that it could open the door to developing specific personalized drugs against this pathology.
The new animal model has made it possible for the first time to develop T-cell lymphomas that are very similar to those in patients, which will make it easier to identify weak points in lymphomas , design drugs and test their effectiveness before starting clinical studies in humans.
The work, in which researchers from the University of Salamanca, the CSIC and the CIBERONC have also collaborated, has been financed by the “La Caixa” Foundation, the Spanish Association against Cancer (AECC), the Ministry of Science and Innovation, the Carlos III Health Institute and the Junta de Castilla y León.