U-RT1 – A new model for Richter transformation

• Main Authors: Teresa Schmid, Julia Maier, Melanie Martin, Alpaslan Tasdogan, Eugen Tausch, Thomas F.E. Barth, Stephan Stilgenbauer, Johannes Bloehdorn, Peter Möller, Kevin Mellert
• Format: Article
• Language: English
• Published: Elsevier 2021-01-01
• Series: Neoplasia: An International Journal for Oncology Research
• Subjects: Richter transformation; Richter syndrome; In vitro model; CLL; DLBCL
• Online Access: http://www.sciencedirect.com/science/article/pii/S1476558620301780

The advent of highly effective treatments targeting the disease biology of chronic lymphocytic leukemia (CLL) has transformed the therapeutic field tremendously. However, transformation into an aggressive B-cell lymphoma, called Richter syndrome (RS), remains highly challenging since the treatment options for this condition are still insufficient. Exploratory drug testing and experimental studies are restricted by the lack of satisfactory models. We have established U-RT1, a cell line derived from a highly proliferating RS clonally related to the patient's underlying CLL. The cell line shows morphological features and an immunophenotype of RS-DLBCL (non-GCB). Molecular analysis revealed a complex karyotype with driver aberrations characteristic for RS such as loss of TP53 and CDKN2A. Furthermore, U-RT1 displays a chromosomal gain of the NOTCH1 gene locus and strong immunoreactivity for BCL-2. These features suggest that U-RT1 is the first eligible model system for investigations on the pathogenesis of RS and novel treatment options.