Discovery of how a type of myelodysplastic syndrome functions 

A team of scientists from Cima and the Clínica Universidad de Navarra has achieved a better understanding of how a rare blood disease occurs: myelodysplastic syndrome with deletion in the long arm of chromosome 5 (5q MDS or 5q- syndrome). The results, published in Nature Communications, reveal new clues about the mechanisms of the disease and how it responds to conventional treatment with lenalidomide.

The deletion is a type of DNA lesion and, in the case of 5q- syndrome, it manifests itself with the lack of a part of the long arm (q arm) of human chromosome 5, which affects myeloid cells in the bone marrow.

The research, part of the Cancer Center Clínica Universidad de Navarra (CCUN), has analyzed in detail the bone marrow stem cells of patients with this type of syndrome using a single-cell sequencing technique. “The most surprising aspect of this study is that both cells with deletion in 5q and those without it present similar alterations in gene activity,” as explained by Dr. Mikel Hernáez, researcher on the project and director of the Computational Biology and Translational Genomics Program at Cima. 

As Dr. Felipe Prósper, co-director of the Hemato-Oncology Program at Cima and of the Hematology and Hemotherapy Service at the Clínica Universidad de Navarra, adds, “our work indicates that all marrow cells, regardless of whether or not they have the deletion, contribute to abnormal blood formation in these patients”. 

The scientists have also discovered that the deletion in 5q deregulates certain key genes, which could be why cells with the deletion play a greater role in the symptoms of the disease. “In patients who responded well to lenalidomide, the drug corrected many of the problems in gene activity in both deletion and non-deletion cells. But some alterations persisted, which may explain why some patients eventually relapsed. Those who did not respond to the treatment is because lenalidomide could not reverse the alterations in gene activity,” Dr. Teresa Ezponda, a scientist at Cima and one of the principal investigators of the study, concludes.

These findings help to better understand how this myelodysplastic syndrome works and how it responds to lenalidomide. The scientists hope that these results will serve to develop more effective and personalized therapies for this blood disease.

This research is part of the Navarra Health Research Institute (IdiSNA) and the Center for Biomedical Research in Cancer Network (CIBERONC), with the participation of 12 members belonging to two CIBER groups, one of them led by Dr. Felipe Prósper. It has also received public and private funding from various entities including the Government of Navarra, the Carlos III Health Institute, the Ministry of Science, Innovation and Universities, the “la Caixa” Foundation, and Iberdrola, through the Spanish Association Against Cancer, (EDITOR project), in the call for Accelerator Grants, awarded in coordination with Cancer Research UK (CRUK) and Fondazione AIRC per la Ricerca sul Cancro (AIRC).