Thursday, December 2

Mutations That Cause High-Mortality Blood Cancer Sequenced

Cells seen under the microscope.

Spanish researchers have completed a catalog of mutations of a gene present in peripheral T-cell lymphoma, a type of tumor that affects white blood cells aggressive, high mortality and for which there are no effective treatments.

The study, led by researchers from the Cancer Research Center, a joint center of the Higher Council for Scientific Research and the University of Salamanca (CIC-CSIC-USAL), has been published in the EMBO Journal.

The work has identified the different types of mutations that cause uncontrolled activation of the VAV1 gene, which can contribute to develop specific drugs personalized against this pathology.

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 dangerousEither 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, these positive functions become harmful and cause them to proliferate uncontrollably and generate lymphomas.

In this work, the researchers have shown that 51% of mutations that affect the VAV1 gene promote its uncontrolled activation and that these alterations they 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 underscores the fact that lthe presence of these mutations is not trivial, but they are the main responsible for the origin of the tumor “, points 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 generate lymphomas in mice after expression of VAV1 mutants in healthy T lymphocytes. 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 specific 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 funded 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.

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