A work of the Higher Council for Scientific Research (CSIC) system could provide a more accurate diagnosis for variant sporadic Burkitt's lymphoma, a highly aggressive tumor growth and that affects the lymphatic system and, in the absence of treatment, is fatal in a few months. The investigation, which is published in Cancer Research, could lead to the development of more targeted therapies and less toxic than those currently used.
The study is the work of the researcher Private-CSIC Irene Molina, also under the direction of the CSIC researcher Miguel R. Campanero, Instituto de Investigaciones Biomédicas Alberto Sols (CSIC joint center and the Autonomous University of Madrid). Scientists have counted on the participation of Miguel Angel Piris group, the National Cancer Center, and Javier Menárguez, Hospital Gregorio Marañón in Madrid.
As explained Campanero, the Burkitt lymphoma or leukemia is a rare form of cancer of the lymphatic system (part of the so-called non-Hodgkin's lymphoma) that usually occurs among children and youth, although occasionally seen in adults. In fact, its endemic variation affects mainly equatorial Africa and is one of the most common diseases among children. The sporadic variant, however, is between 40 and 50% of non-Hodgkin lymphomas in the industrialized countries.
Researchers have studied this second type of the disease, which presents two problems: firstly, its diagnosis is based on several complementary approaches, which are not always completely reliable, so often confused with other types of lymphoma. Otherwise, therapy is based on a very aggressive treatment and intensive chemotherapy, which includes various combinations of anti-tumor agents.
According to researchers at the CSIC, the toxicity of treatment is important because it presents, among its side effects, neurotoxicity, hematologic toxicity, mucositis severe heart disease and infertility.
"The development of anti-tumor therapy with low toxicity depends, generally, the identification of proteins whose expression or function are altered specifically in target cells. It is necessary to know the molecular mechanisms involved in the formation of each tumor," Campanero points. He adds: "The mechanisms involved in the formation of sporadic Burkitt lymphoma have barely been studied so far." This was precisely the research group.
Campanero team noted that one of the active members of the family of E2F transcription factors, the E2F1, has very high levels of expression in all biopsies from patients with Burkitt's lymphoma tested, compared with the levels detected in tissues not tumor. From this finding, the authors suggest that detection of a level similar to the expression of E2F1 is not detected in tumor tissues serve to exclude a diagnosis of pathology.
On the other hand, the researchers used different CSIC specific interfering RNA of E2F1 to inhibit the expression of E2F1 in cells affected by this tumor type. Their findings indicate that reducing the expression of this protein in cells of sporadic Burkitt lymphoma, not only inhibits growth and proliferation but also inhibits their ability tumor.
"Given that the expression of E2F1 is not required for the proliferation of most normal cells, research suggests the generation of tools to inhibit the expression of E2F1 in patients of this type of lymphoma. These tools could be used for development therapy less toxic than currently used for the treatment of this disease, "concluded the researchers of the CSIC.