An ibs.GRANADA investigation identifies genes that allow advances in lymphoma treatment

The finding, on which the team led by Pedro Medina from the Center for Genomics and Oncology Research (GENYO) has been working since 2014, focuses on mutations that to date had gone unnoticed by the scientific community.

Science has taken another step to be able to treat lymphomas. A group of researchers from the Ae22-Cancer Genetics, Biomarkers and Experimental Therapies group at ibs.GRANADA and the Center for Genomics and Oncology Research (GENYO) at the Health Technology Park (PTS) in Granada, led by carcinologist Pedro Medina Vico , has managed to find genes that are essential for the mutation of this type of cancer in its diffuse variant of B cells. In this way, by identifying them together with mutations that have gone unnoticed by the scientific community until now, the treatment against this disease is possible to improve it by being able to focus on this aspect.

The work, published in the medical journal Blood and developed since 2014, has been possible thanks to a doctoral student who wrote a thesis in which part of the research was based on the activity of the BCL7A gene. So, it was found that this gene was capable of curbing lymphoma, one of the most common types of blood cancer of our times. Based on this finding, this research has been developed that opens the door to improve treatments against this disease. According to Pedro Medina Vico, the aforementioned gene is key because "lymphomas accumulate mutations in BCL7A to prevent it from working properly and stop its development."

In other words, this cancer tries to deactivate the part of the genome that is capable of stopping it and that is why the work has focused on understanding how it happens in order to tackle the problem. “When we observed that BCL7A accumulated mutations in splice sites, and that these mutations had gone unnoticed by the rest of the scientific community, we thought that other genes could have followed the same fate”, explains Medina Vico. The splicing sequences are essential for new gene products to be created, which in this case make it possible to stop cancer growth. Research has discovered that the mutations that accumulate in these areas affect the clinical picture of the patient, so it is convenient to focus on them.

In a didactic way, Pedro Medina Vico explains that "the cut and splice sequences are part of the so-called non-protein coding sequences", whose importance is very high. It is because in other investigations it has been discovered that some of these sequences generated tumors that disappeared if they stopped having activity. So if they are removed or stopped, the chances of a cure increase. A finding that is very important because it improves the chances of receiving personalized treatment based on the genome of the lymphoma that the person suffers.

hard work

Beyond research as such, this work has also served to highlight the efforts of the scientific community. “It has been a great satisfaction, because it has cost us a lot of effort, and it has had doctoral student Álvaro Andradres as its first author. For me it is a great satisfaction to see how Álvaro, who was already a student of mine in the Biochemistry degree at the University of Granada, comes to my laboratory without knowing anything about research, and ends up publishing an article in the best scientific journal in his area. ”. A titanic effort that has led them to investigate in this line since 2014 in collaboration with other scientists from the CIMA in Navarra and the CNIC and CNIO in Madrid.

Unlike other investigations related to lymphomas, the finding of these scientists from Granada has been novel because they have discovered that many important genes for the development of lymphomas accumulate mutations in the cut and splice sites and therefore should not be ignored. Something that was happening to date, in part because DNA remains largely unknown to the point that these sequences are known by the scientific community as "the dark side of the genome."

However, this research opens a very relevant field towards a better treatment of lymphoma. "This work may have direct clinical applications since we have discovered that mutations in the CD79B gene's cutting and splice sites have a functional impact", assures Pedro Medina Vico. "Which helps doctors to determine the treatment of patients and to choose specific drugs (such as ibrutinib) to treat patients more effectively." A starting point to think that in the future it may be possible to cure lymphoma. “The tumors that are easy to cure have already been cured, now we have to work with the more complicated ones. This work is also important because it has been developed on one of the lymphomas with the worst prognosis, diffuse large B-cell lymphoma, and allows us to learn more about how they are generated”.

Fragile financing

In addition to the investigative task, the fragile situation of science in Spain means that these scientists have to regularly seek funding in order to continue with their work. Something that has also happened to the Medina Vico team. “Unfortunately, I spend a large part of my time looking for financing. Time that could be spent more productively researching. We have received most of the money that finances my laboratory through the Junta de Andalucía or private entities such as the Spanish Association against Cancer”. On the contrary, the support of the central government has been "very scarce" to the point that "if this work had depended on the financing that the Government of Spain has granted us, this project, which has been published in the best magazine in the world in his field, he would never have seen the light”.

“Spanish society should “force” its politicians to invest at least 3% of their GDP in science, as the countries we want to emulate such as Germany, Switzerland, or Sweden do, and not 1.25% as it does Spain”, argues Medina Vico. "We have to change the mentality and we have to understand that countries are rich because they invest in science." A conviction that is part of the scientific motivation to continue research. In this case, the next step will be to continue with the work already started. “We are trying to unravel more about these types of mutations and about the BCL7A gene. Everything will depend on whether we have adequate financing. At the moment we are waiting for the resolution of a project that we have requested from the Government of Spain, we hope to have your support”. A problem that, he says, would not have in countries like the United States.