An international team of researchers has completed the map of genetic changes in chronic lymphocytic leukemia (CLL). This tool will provide a better understanding of the disease and can lead to more accurate prognoses for patients, improved diagnoses and the development of new treatments.
The work, published in the journal “Natural Genetics”, and is coordinated by researchers from IDIBAPS-Hospital Clínic and the University of Barcelona, University of Oviedo, all from CIBERONC; Dana-Farber Cancer Institute and the Broad Institute of MIT and Harvard University, Boston; and the University of Ulm in Germany.
Chronic lymphatic leukemia (CLL) is a type of blood cancer and It is the most common type of leukemia in the Western world, with an incidence of approximately 5 cases per 100,000 population per year. It is characterized by an increase in the number of B lymphocytes, a type of white blood cells, which can be detected incidentally during routine blood tests.
CLL can be slow growing with a good prognosis or fast and aggressive. Knowledge of the molecular alterations that cause this very different evolution could allow Know the prognosis early. Previous studies have provided fragments of a CLL map, each focused on particular types of patients or with limited data.
“The goal of this study was to provide a virtually complete catalog of all genomic alterations that cause CLL and its molecular subtypes. It was a huge effort of a large international team that has analyzed the genome of more than 1,000 patients using new bioinformatics tools for more than 4 years,” he explains. the Aragonese Elías Campo (Boltaña, Huesca, 1955), co-lead author of the studyhead of the molecular pathology of lymphoid neoplasms group at IDIBAPS and researcher at CIBERONC.
More than a hundred new genes involved
To construct the CLL map, the researchers analyzed variations in genetic sequences, gene expression patterns and chemical modifications of DNA (genomic, transcriptomic and epigenomic data). of 1,148 patients.
The study identified 202 genes (including 109 new ones) which, when mutated, they can lead to disease onset and progression. The characterization of the subtypes of this leukaemia, which differ in their genomic characteristics and their clinical evolution, has also been perfected. “Beyond the genetic sequences, the expression patterns of certain genes allowed us to subcategorize the disease, which provides very valuable prognostic information,” explains Xose S. Puente, a researcher at the University Institute of oncology from the University of Oviedo and CIBERONC and co-lead author of the study.
Patients’ clinical outcomes were associated with the genomic, transcriptomic and epigenomic characteristics of their tumor, as well as integration of this data can predict the likelihood that a patient will have a disease very indolent for many years, in remission after treatment, or the possibility that your leukemia is more aggressive and requires further treatment.
The results of this study may have a a significant impact on clinical practicesince “the new map will allow us to compare the genomic characteristics of new patients with data from patients with similar genetic profiles and know what their evolution and response to treatment has been,” explains Iñaki Martín-Subero, co-head of File author of the study, head of the biomedical epigenomics group at IDIBAPS and researcher at CIBERONC.
An open search tool
One of the objectives of the study is that this information be used by the scientific community to progress in the treatment of this disease. To do this, the map identified in this study has been transformed into an interactive web portal so that researchers around the world can use it as a resource in their research and advance their understanding of the causes and characteristics of the different subtypes of LLC.
“The new LLC card allows us to move towards precision medicine in this disease, as it can help us tailor the prognosis and treatment of a new patient more precisely based on their particular molecular characteristics,” concludes Elías Campo.