12_6_21_CIMA_Un trabajo demuestra por primera vez el papel de las células madre hematopoyéticas en el origen de los linfomas B
A work demonstrates for the first time the role of hematopoietic stem cells in the origin of B lymphomas.
Researchers from CIMA of the University of Navarra and the CIC of the University of Salamanca/CSIC have developed mice with a modification Genetics that will be used to evaluate new therapeutic strategies for very aggressive lymphomas.
Scientists at research center Applied Medicine (CIMA) of the University of Navarra and of the research center of Cancer (CIC), of the CSIC and the University of Salamanca, have demonstrated that a protein, called MALT1, is involved in the development of MALT lymphomas. The results of work have been published in the scientific journalProceedings of the National Academy of Sciences of the United States of America (PNAS).
In this work, researchers have generated a new transgenic mouse model that develops lymphomas with the main features of human MALT lymphoma. "To date it has not been possible to develop experimental models of this disease in the laboratory, so these mice will be an essential tool to study the biology of these lymphomas and to evaluate new therapeutic strategies," explains Dr. José A. Martínez-Climent, researcher of the laboratory Molecular Oncology of CIMA and co-director of the study, together with Dr. Isidro Sánchez García, researcher of laboratory Experimental Therapeutics and Translational Oncology of the CIC of Salamanca.
One of the most remarkable aspects of this work is that the animal model is based on a modification Genetics induced in hematopoietic stem cells. "The results suggest that these cells may be involved in the development of mature B lymphomas, something that has not been accepted by the academic community and is the subject of continuous discussion", states the researcher of the CIMA. "This and similar models will allow us to continue to investigate the role of these cells in the origin of lymphoid neoplasms."
B-cell lymphomas are the third fastest growing cancer subject in recent years, after melanoma and lung cancer. Among them, MALT lymphoma accounts for 8 percent and, unlike other lymphomas, it is not located in the lymph nodes but in the stomach, lung, salivary glands, intestine, skin and thyroid.
In the study, the researchers have induced a second modification Genetics that inactivates the P53 gene and induces the development of some very aggressive tumors, the lymphomas subject activated lymphocytes. According to Martínez-Climent, "they account for 15% of all lymphomas, and patients have a poor response to current therapies. Therefore, it is necessary to develop selective therapies that are effective in this specific pathology. We believe that the use of MALT1 inhibitor drugs may represent one of the most promising therapies for these patients.
The murine model result of the work coordinated between the CIMA of the University of Navarra and the CIC of the University of Salamanca has materialized in a patent, which will be developed by the business biotechnology company Digna Biotech. As Dr. Martínez-Climent explains, "we intend to continue the development of molecules that inhibit MALT1 more effectively and serve to treat these aggressive lymphomas. The final goal is to be able to evaluate these drugs in clinical trials in patients with lymphoma". In this sense, the two groups are collaborating with Dr. Lorena Fontán, co-author of work who is currently working at Weil Cornell Medical Center (New York), to evaluate small molecules that inhibit MALT1 activity in our mice.
Dr. Carolina Vicente-Dueñas, from the CIC of the University of Salamanca, and Dr. César Cobaleda, from the Centro de Biología Molecular Severo Ochoa/CSIC at the Universidad Autónoma de Madrid, together with other national and international clinicians and researchers, have participated in the work .