The leukemia is the second blood cancer with higher prevalence, and according to the latest report from the Spanish Network of Cancer Registries on the estimates of this disease in Spain, in this year 2023 6,411 people will have been diagnosed with leukemia.
A new study carried out by an international team of scientists and in which researchers from the Cima Universidad de Navarra and scientists from the University of Cambridge have participated has described for the first time specific mechanisms of leukemia that prevent the development of healthy cells and promote their evolution. Their findings have been published in the scientific journal Nature Genetics and will contribute to the development of new therapies for patients.
Researchers have used cutting-edge technologies to analyze the differences that exist in the generation of healthy blood cells versus leukemic blood cells. This has allowed them to discover that leukemic cells deteriorate the gene regulation mechanisms that healthy cells use to determine when and to what extent a gene is activated or deactivated (gene expression), and this prevents them from evolving into mature healthy cells and favors the tumor growth. The importance of analyzing this process lies in the fact that gene regulation determines whether the identity that the cells will take is a healthy cell or a leukemic cell.
Leukemic cells prevent the evolution of healthy cells
The process of formation of blood cells (hematopoiesis) begins in hematopoietic stem cells, which are capable of generating the different types of blood cells (white blood cells, red blood cells and platelets). Specifically, it is in chromatin (the mixture of DNA and proteins that make up chromosomes) where the genetic regulation processes occur that give rise to the great variety of cell types present in the blood. Two groups of proteins called chromatin factors and transcription factors are involved in these processes.
“Identifying a new therapeutic route for leukemia is very important because, for example, in acute myeloid leukemia only 15% of those affected survive more than five years”
Transcription factors mark the specific genes to be activated in each cell type, and chromatin factors regulate the expression of these genes through changes in the biochemical structure of chromatin. In this way, the identity of the blood cells is determined. The deregulation of these processes triggers different blood cancerswith leukemia being the second most common.
Until now, the role that chromatin factors played in determining cell identity was unclear. However, the team of Cima and Cambridge researchers has shown that chromatin factors are a crucial element in the regulation of cell identity. For this, cutting-edge technologies have been used. CRISPR and single cell.
“Thanks to the use of a technology that allows us to study individual cells, we have demonstrated the complexity of the processes that regulate cells, revealing a great diversity in the function of chromatin factors, as well as other functions shared with transcription factors,” they explain. Julen Mendieta y Ainhoa Goñifirst authors of the study and researchers of the Cima Hemato-Oncology Program, integrated into the Cancer Center Clínica Universidad de Navarra.
A way to develop new treatments against leukemia
By studying the processes that regulate cell identity in leukemia, the researchers revealed how leukemic cells corrupt the normal functions of chromatin factors to block evolution toward healthy cell types and facilitate tumor growth. They also observed that in this alteration new complexes of transcription factors and chromatin factors exclusive to leukemic cells were formed.
“As these complexes are specific to leukemia and are not necessary for normal hematopoiesis, they are an ideal target for therapy that can deactivate them without causing any other harm to the patient, unlike current treatments such as chemotherapy, with high levels of toxicity,” says David Lara Astiaso, researcher at the Department of Hematology at the University of Cambridge and lead author of the study.
The teacher Brian Huntly, director of the Department of Hematology at the University of Cambridge and co-director of the study, highlights that “identifying a potential new therapeutic avenue for leukemia is especially important. For example, in acute myeloid leukemia, which is the most common in adults and very aggressive, only 15% of people diagnosed with this disease survive more than five years.”
Fuente: Top University of Navarra