Mice Overexpressing Wild Type RRAS2: A Novel Preclinical Model for Testing Anti-Chronic Lymphocytic Leukemia Therapies

• DOI: 10.20944/preprints202309.1417.v1
• Publication Date: 2023-09-25T08:20:59Z
• Authors: Balbino Alarcón; Alejandro M. Hortal; Ana Villanueva; Irene Arellano; Cristina Prieto; Pilar Mendoza; Xose R Bustelo
• Keywords: Venetoclax

B-cell chronic lymphocytic leukemia (B-CLL) is the most common type of in Western world. Mutations different genes, such as TP53 and ATM, deletions specific chromosomal regions, including 11q or 17p, have been associated with a worse prognosis for disease. Recent research from our group has demonstrated that, contrary to usual cancer development process through missense mutations, B-CLL driven by overexpression small GTPase RRAS2 its wild-type form, without activating mutations. While some mouse models this disease developed date are commonly used research, they come various disadvantages, long waiting period until fully develops, need cell engraftment, or, cases, failure replicate alterations found human patients. We recently introduced Rosa26-RRAS2fl/flxmb1-Cre new model full penetrance. In work, we validated novel tool therapies testing two widely applied targeted agents: ibrutinib venetoclax. This also paves way agents against R-RAS2 itself, an approach that not yet explored clinical practice.