Hortal, A.M.; Villanueva, A.; Arellano, I.; Prieto, C.; Mendoza, P.; Bustelo, X.R.; Alarcón, B. Mice Overexpressing Wild-Type RRAS2 Are a Novel Model for Preclinical Testing of Anti-Chronic Lymphocytic Leukemia Therapies. Cancers2023, 15, 5817.
Hortal, A.M.; Villanueva, A.; Arellano, I.; Prieto, C.; Mendoza, P.; Bustelo, X.R.; Alarcón, B. Mice Overexpressing Wild-Type RRAS2 Are a Novel Model for Preclinical Testing of Anti-Chronic Lymphocytic Leukemia Therapies. Cancers 2023, 15, 5817.
Hortal, A.M.; Villanueva, A.; Arellano, I.; Prieto, C.; Mendoza, P.; Bustelo, X.R.; Alarcón, B. Mice Overexpressing Wild-Type RRAS2 Are a Novel Model for Preclinical Testing of Anti-Chronic Lymphocytic Leukemia Therapies. Cancers2023, 15, 5817.
Hortal, A.M.; Villanueva, A.; Arellano, I.; Prieto, C.; Mendoza, P.; Bustelo, X.R.; Alarcón, B. Mice Overexpressing Wild-Type RRAS2 Are a Novel Model for Preclinical Testing of Anti-Chronic Lymphocytic Leukemia Therapies. Cancers 2023, 15, 5817.
Abstract
B-cell chronic lymphocytic leukemia (B-CLL) is the most common type of leukemia in the Western world. Mutations in different genes, such as TP53 and ATM, and deletions in specific chromosomal regions, including 11q or 17p, have been associated with a worse prognosis for the disease. Recent research from our group has demonstrated that, contrary to the usual cancer development process through missense mutations, B-CLL is driven by the overexpression of the small GTPase RRAS2 in its wild-type form, without activating mutations. While some mouse models of this disease have been developed to date and are commonly used in B-CLL research, they come with various disadvantages, such as a long waiting period until the leukemia fully develops, the need for cell engraftment, or, in some cases, a failure to replicate the alterations found in human patients. We have recently introduced Rosa26-RRAS2fl/flxmb1-Cre as a new mouse model of B-CLL with full disease penetrance. In this work, we have validated this mouse model as a novel tool for the development of new therapies for B-CLL by testing two of the most widely applied targeted agents: ibrutinib and venetoclax. This also paves the way for the development of new targeted agents against R-RAS2 itself, an approach that has not yet been explored in clinical practice.
Keywords
R-RAS2; RAS; GTPases; chronic lymphocytic leukemia; B-CLL; mouse model; ibrutinib; venetoclax; new therapies; cancer treatment
Subject
Medicine and Pharmacology, Oncology and Oncogenics
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
