An international team of researchers has completed the map of genetic changes in the chronic lymphatic leukemia (LLC). This tool will provide a better understanding of the disease and may lead to more accurate prognoses for patients, better diagnoses and the development of new treatments.
The work is published in the journal Natural genetics and it 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 leukemia 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 and prognostic, or fast-growing and aggressive. Knowledge of the molecular alterations at the origin of this very different evolution could make it possible to know the prognosis at an early stage. Previous studies have provided fragments of a CLL map, each focused on particular types of patients or with limited data.
“The objective of this study was to provide a virtually complete catalog of all genomic alterations responsible for CLL and its molecular subtypes. It was a huge effort by a large international team that analyzed the genome of more than 1,000 patients using new bioinformatics tools for more than 4 years,” he points out. Elias Campoco-lead author of the study, head of the molecular pathology of lymphoid neoplasms group at IDIBAPS and researcher at CIBERONC.
More than a hundred new genes implicated in the onset of the disease
To construct the CLL map, researchers analyzed variations in genetic sequences, gene expression patterns and chemical modifications of DNA (genomic, transcriptomic and epigenomic data) from 1,148 patients.
The study identified 202 genes (including 109 new ones) which, when mutated, 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 profiles of certain genes allowed us to subcategorize the disease, which provides very valuable prognostic information,” he explains. Xose S. Puenteresearcher at the University Institute of Oncology of 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, so integration of these data can predict the likelihood of a patient having highly indolent disease for many years, remission after treatment or the possibility that your leukemia is more aggressive and requires new treatments.
The conclusions of this study may have an important impact on clinical practice, since “the new map will allow us to compare the genomic characteristics of new patients with data from patients with similar genetic profiles and to know their evolution and their response to treatments, ” Explain Inaki Martin-Suberostudy co-lead author, group leader Epigenomics biomedical at IDIBAPS and researcher at CIBERONC.
An open search tool
One of the goals of the study is for this information to be used by the scientific community to advance 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 CLL map allows us to move towards precision medicine in this disease, as it can help us tailor a new patient’s prognosis and treatment more precisely based on their particular molecular characteristics,” concludes -he. Elias Campo.