Mutation in the NOTCH1 gene influences aggressive course of blood cancer
Researchers at Ulm University Hospital have discovered a mutation in the non-coding area of the NOTCH1 gene that significantly exacerbates the course of chronic lymphocytic leukemia (CLL), the most common form of blood cancer. The findings, published in the journal Blood, show that such DNA segments, which have received little attention so far, play a central role in understanding diseases. In the future, the mutation could serve as a biomarker to determine the optimal time for therapies in CLL patients.
The study, led by Prof. Franz Oswald from the Department of Internal Medicine I , examined clinical data from CLL patients and found that the mutation alters the RNA of the NOTCH1 gene. This leads to the formation of a new protein, NOTCH1-152, which blocks degradation processes and stabilizes the normal NOTCH1 protein. This overrides control mechanisms that inhibit cancer growth. The result is an accelerated course of the disease with poorer chances of survival. Patients in whom CLL develops symptoms more quickly, which requires early treatment with risks and a less favorable prognosis, are particularly affected.
By using modern analytical methods such as CRISPR-Cas9 and AI-supported programs, the researchers were able to understand the molecular mechanisms of the mutation. The discovery highlights the importance of non-coding DNA regions that have often been overlooked until now. As a biomarker, NOTCH1-152 could help to monitor patients with an aggressive course of the disease more closely and to initiate targeted therapies to avoid risky developments such as the Richter transformation. Other scientists from Ulm, the DKFZ, the Charité, the University of Giessen, the University Hospital of Cologne and the German Red Cross were involved in the study.
Original Paper:
Min Guo, Tugba Memis, Alena Sophie Ehrmann, Anselm Pittrof, Bernd Baumann, Francesca Ferrante, Eugen Tausch, Kirsten Fischer, Hartmut Döhner, Tilman Borggrefe, Stephan Stilgenbauer, Ulrich Pannicke, Klaus Schwarz, Daniel Mertens, Franz Oswald (2025): A noncoding mutation in the NOTCH1 gene initiates oncogenic NOTCH signaling via wild-type NICD stabilization in CLL. Blood. DOI: 10.1182/blood.2025028529
Editor: X-Press Journalistenbüro GbR
Gender Notice. The personal designations used in this text always refer equally to female, male and diverse persons. Double/triple naming and gendered designations are used for better readability. ected.
Most read
One Health: New approach to early detection of pandemics through wildlife surveillance A groundbreaking study by the Hebrew University of Jerusalem proposes to use wild animals as an earl...- Neutrophils: New therapeutic approach against cancer discovered Researchers at the Faculty of Medicine at the University of Duisburg-Essen have developed a promisin...
- New findings on heart attacks: Focus on overactive platelets Researchers at the Augsburg University Medical Center have identified a subgroup of particularly act...
