Down syndrome is the most common human genetic disorder with a frequency of one in every 700 newborns in the USA. It is caused by the acquisition of a third copy of chromosome 21, a phenomenon called trisomy 21. The consequences of trisomy 21 include mild to severe cognitive impairment, congenital heart defects and other health issues, like an increased risk of developing myeloid leukemia of Down Syndrome (ML-DS), a pediatric blood malignancy.

While prognosis is good for most patients, a fraction does not respond well to standard chemotherapy, which is particularly toxic to Down syndrome patients, stressing the need for alternative therapeutic approaches.

Previous research in the field identified the genes that are most frequently mutated in ML-DS. Many of these happen to encode important regulators of gene expression, this is, genes controlling other genes’ activity. Unexpectedly, those in charge of organizing the three-dimensional structure of the DNA inside the cell nucleus seem to be particularly affected in this type of leukemia.

Dr. Cuartero and his team are confident they can shed new light on how these alterations produce the malignant transformation to ML-DS and how they cooperate with trisomy 21, which would help explain the high incidence in Down Syndrome children. The researchers hope this knowledge will help to identify new druggable targets to fight ML-DS and lay the foundations for the development of new therapies in the future.

The American Society of Hematology (ASH) is the world’s largest professional society of hematologists dedicated to furthering the understanding, diagnosis, treatment, and prevention of disorders affecting the blood. The deserving awardees of the 2022 ASH Global Research Award receive support to conduct their research in their home countries to contribute to the global hematology research workforce.