Dysregulation of genes responsible for higher leukemia risk in children with Down syndrome Biochemical analysis lays foundation for treatment development ScienceDaily

[ad_1]

People who have a third copy of chromosome 21, known as trisomy 21, are at increased risk of developing acute myeloid leukemia (AML), an aggressive form of blood cancer. Scientists led by the Department of Pediatrics at the University Hospital Frankfurt have now identified the cause: although the extra chromosome 21 causes an overdose of genes for many genes, above all a disorder of the RUNX1 gene – the gene that regulates many others – seems to be It is responsible for causing acute myelogenous leukemia (AML). Targeting the disordered regulator could pave the way for new therapies.

Leukemia (cancer of the blood) is a group of malignant and aggressive diseases that affect the blood-forming cells in the bone marrow. Very intensive chemotherapy and in some cases bone marrow transplantation is the only treatment. Like all cancers, leukemia results from changes in DNA, the genetic material found in human cells in the form of 46 chromosomes. In many forms of leukemia, large parts of these chromosomes are altered. People with Down syndrome, who have three copies of chromosome 21 (trisomy 21) have a very high risk of developing acute myeloid leukemia (AML) in the first four years of their lives more than 100 times as high as children with Down syndrome. Down syndrome is the most common congenital genetic disorder, affecting 1 in 700 newborns.

The RUNX1 transcription factor is responsible

The research group led by Professor Jan Henning Clausmann, Director of the Department of Pediatrics and Adolescent Medicine at the University Hospital Frankfurt, has discovered how the extra chromosome 21 can promote AML. With the help of genetic scissors (CRISPR-Cas9), they screened each of the 218 genes on chromosome 21 for its carcinogenic effect. It turns out that RUNX1 The gene responsible for the carcinogenic properties of the chromosome. In further analyses, the researchers were able to confirm that only one particular variant — or isoform — of the gene promotes leukemia development. Klossman explains: “Other RUNX1 The isoforms were even able to prevent the cells from deteriorating. That explains RUNX1 It has not yet emerged – in several decades of intense cancer research.”

the RUNX1 The gene encodes a “transcription factor” – a protein responsible for regulating the activity of other genes. RUNX1 regulates many processes, including embryonic development and early and late hematopoiesis, or hematopoiesis. The disruption of this important regulator is thus a major event in the development of AML. “Thanks to the results of our research, we now have a better understanding of what happens in the process of leukemia formation,” explains Klossmann, an expert in pediatric cancer. “The study underscores how important it is to screen all genetic variants in carcinogenesis. In many cases, certain mutations in cancer cells change how these variants form,” he says.

Developing more advanced treatment approaches

These insights are important for a better understanding of the complex mechanisms of carcinogenesis, explains Klossmann: “In this way, we have laid the foundation for developing more advanced therapeutic approaches. Through our biochemical analyses, we now know exactly how a genetic variant alters blood cells. From there, we have been able to use materials certain hindering disease mechanism.” The goal now is to further explore the effect of these substances for use in medical care. Klusmann: “Based on our experience, we now want to develop treatments to correct this imbalance. Their implementation in clinical practice will certainly take a few more years, but hopefully in the future they will lead to sparing our young patients intensive chemotherapy.”

[ad_2]

Source link

Related Posts

Precaliga