Chronic Lymphocytic Leukemia: National Center Researchers Identify New RNA Markers

23 July 2025, Padua – A groundbreaking international study led by National Center researchers has uncovered new molecular markers that may transform the diagnosis and treatment of chronic lymphocytic leukemia (CLL), the most common type of leukemia in adults in the Western world.

Led by University of Padua Professor Stefania Bortoluzzi, and recently published in the prestigious Journal of Hematology & Oncology, researchers have identified two circular RNA molecules—circCORO1C and circCLEC2D—as potential biomarkers for the most aggressive forms of CLL.

Unlike traditional linear RNA, circular RNAs form a unique closed-loop structure that makes them highly stable and resistant to degradation by exonucleases, a feature that positions them as promising biomarkers for disease diagnosis and potential therapeutic targets. The study focused on a rare and aggressive CLL subtype characterized by chromosomal abnormalities leading to overexpression of the BCL3 protein, which represents about 1% of all diagnosed cases. Using RNA therapeutics to study rare diseases, often described as orphan diseases, represents a paradigm shift in medicine. It moves away from a “one-size-fits-all” model toward precision and speed, offering hope to patients with conditions long ignored by traditional pharmaceutical pipelines. With the growing capabilities in genomics, bioinformatics, and RNA delivery, we are entering an era where even the rarest diseases may soon have a treatment path.

“This discovery could mark a turning point,” said Prof. Bortoluzzi of the Department of Surgery, Oncology, and Gastroenterology. “These circular RNAs may serve as biomarkers of disease aggressiveness and a launching point for future therapeutic targets in RNA-based medicine.”

Prof Bortoluzzi and research team

From Spoke 6 – RNA Drug Development of the National Center, Prof. Stefania Bortoluzzi and Dr. Andrea Visentin coordinated the study, which involved analyzing patient samples using advanced sequencing technologies and computational modeling. Their work was made possible thanks to the contributions of two young National Center researchers, Eleonora Roncaglia and Enrico Gaffo.

“This study demonstrates the strength of international collaboration,” said Dr. Visentin of the Department of Medicine. “Studying such a rare and complex disease required the combined efforts of 28 institutions across 12 countries, including Sweden, Greece, the U.S., and China.”

The research initiative was made possible thanks to support from the University of Padua’s STARS Project, the AIRC Foundation for Cancer Research, PNRR funding, the National Center for Gene Therapy and RNA Drugs, and the National Centre for HPC, Big Data, and Quantum Computing. Additional support came from the association Ricerca per Credere nella Vita, founded by a leukemia patient to advance research and support the University Hospital of Padua’s Hematology Department.

As science continues to delve into the role of non-coding RNAs in cancer, discoveries like this bring new hope for patients facing the most difficult forms of leukemia—and mark an important step forward in personalized medicine.

La Repubblica “Una firma molecolare per la leucemia aggressiva

 

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