In recent years, molecular studies of leukemia and other cancers have focused on the molecular analysis of a layer of information, which provided a partial view.
“This is an unprecedented study in cancer genomic research and highlights the importance of integrating different layers of molecular information for a better understanding of the disease, ” explains Iñaki Martín-Subero, from the August Pi i Sunye r Biomedical Research Institute ( IDIBAPS) and coordinator of the study.
The work, in which 51 researchers from 23 different institutions from 6 countries participated, has unveiled the complete epigenome of chronic lymphatic leukemia, the most common type of leukemia. The work, collected in the journal Nature Medicine , shows more than 500 new alterations in the function of the genome that are specific to this leukemia, which will help in the development of new therapies.
In the course of the work, the scientists discovered, thanks to next-generation sequencing techniques and advanced computational biology tools, (thanks to the collaboration of the Barcelona Supercomputing Center) that the blood of 107 affected by chronic lymphatic lymphatic leukemia shared the same 500 variations in DNA detected and that only three protein families seemed to be responsible for these changes.
‘Knowing the sequence of the genome is not enough to know how it works; In order to know its functions and its regulation, an integrative analysis of multiple epigenetic layers is necessary, ‘explains Martín-Subero.
“The biggest challenge we faced once the data was generated was how to analyze and integrate so many layers of information, and distill information that helps us better understand leukemia. It has been three years of computer analysis to complete the functional map of leukemia ”, explains Renée Beekman, leader of the work.
Experts have been able to accurately identify regions with specific functions. In particular, the dark areas of the genome (previously classified as junk DNA) have been illuminated, and they certainly contain a multitude of regions essential for the genome to function.
In addition to studying leukemia cells, researchers have compared them to healthy cells. “We have seen how the map of leukemia changes compared to the map of healthy cells, and how leukemias are able to create a very efficient molecular infrastructure to grow out of control,” says Beekman.
In addition, the experts discovered that only three protein families seem to be responsible for these variations, a very important fact, since the action of these three protein families can be inhibited with drugs in development.
“This comprehensive map not only allows us to better understand leukemia at the molecular level, but also offers a great source of information for other researchers, with the joint aim of translating the findings into better treatment and a better quality of life for patients patients ”, concludes Martín-Subero.
Reference: Renée Beekman, Vicente Chapaprieta, Jose I. Martin-Subero et al. ‘The reference epigenome and regulatory chromatin landscape of chronic lymphocytic leukemia’. Nature Medicine, May 21, 2018. DOI: 10.1038 / s41591-018-0028-4
