2023-11-02 10:51:14
An international team of researchers from Cima University of Navarra and the University of Cambridge describe for the first time the genetic regulation mechanisms that favor the evolution of the leukemia. In this study, the most exhaustive to date, they have analyzed the differences that exist in the generation of healthy blood cells against leukemic blood cells.
Specifically, they have focused on characterizing the mechanisms of gene regulation that cells use to decide when and to what extent a gene is turned on or off (gene expression). Study This process is very important since gene regulation determines whether the identity that the cells will take It will be that of a healthy cell or celula leucemica.
The authors have revealed that leukemic cells corrupt key gene regulation mechanisms that determine the identity of healthy cells
Using cutting-edge technologies, researchers have revealed that leukemic cells corrupt key gene regulation mechanisms that determine the identity of healthy cells, which blocks their evolution into mature healthy cells and facilitates tumor growth.
The leukemia is he second blood cancer most prevalent. According to the latest report of the Spanish Network of Cancer Registries Based on the estimates of this disease in Spain, in 2023, there will be 6,411 new cases of people diagnosed with leukemia. This finding opens avenues for the development of new treatments for these cancer patients.
The results of this multicenter study are published in the latest issue of the magazine Nature Genetics. Researchers from the University of Salzburg (Austria) and the biotechnology company Relation Therapeutics (United Kingdom) have also collaborated in this work. Several of its researchers belong to the Cancer Network Biomedical Research Center (CIBERONC) and the Health Research Institute of Navarra (IdiSNA).
At the origin of cell formation
The process of formation of blood cells (hematopoiesis) begins in hematopoietic stem cells, which are capable of generating different types of cells blood (white blood cells, red blood cells and platelets).
Specifically, it is in the chromatin (the mixture of DNA and proteins that make up chromosomes) where the processes of genetic regulation 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.
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 cancers, being leukemia the second most frequent.
To demonstrate that chromatin factors are a crucial element in the regulation of cell identity, CRISPR and single cell technologies have been used.
Until now, it was not clear what role the chromatin factors in determining the cellular identity.
However, the team of Cima and Cambridge researchers has shown that chromatin factors are a crucial element in the regulation of cellular identity. For this, technologies have been used CRISPR and single cell.
“Thanks to the use of technology that allows studying single cellswe 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.
From left to right, David Lara and Julen Mendieta, along with other Cima researchers participating in the study. / TOP
Study cell identity in leukemia
Studying the processes that regulate cellular identity in leukemia, This team has revealed how leukemic cells corrupt the normal functions of chromatin factors to block evolution towards healthy cell types and facilitate tumor growth.
In their analysis they observed that in this alteration new complexes of transcription factors and chromatin factors were formed. unique to leukemic cells. “As these complexes are specific to leukemia and are not necessary for normal hematopoiesis, they are an diana ideal for a therapy that can deactivate them without causing any other harm to the patient, unlike current treatments such as chemotherapy, with high levels of toxicity,” he says. David Lara Tablewareresearcher at the Department of Hematology at the University of Cambridge and lead author of the study.
The teacher Brian Huntlydirector 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 it is especially important. For example, in acute myeloid leukemia, which is the most common in adults and very aggressive, only 15% of people diagnosed of this disease survive more than five years”.
Reference:
Lara-Astiaso, David et al. “In vivo screening characterizes chromatin factor functions during normal and malignant hematopoiesis.” Nature genetics (2023)
Rights: Creative Commons.
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