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Mutation in different genes, such as TP53 and ATM, and deletions at specific chromosomic regions, among which are 11q or 17p, have been described to be associated to worse disease prognosis. Recent research from our group has demonstrated that, contrary to what is 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. Some mouse models of this disease have been developed to date and are commonly used in B-CLL research, but they present different disadvantages such as the long waiting period until the leukemia fully develops, the need to do cell engraftment or, in some cases, the fact that the model does not recapitulate the alterations found in human patients. We have recently described Rosa26-RRAS2fl\/flxmb1-Cre as a new mouse model of B-CLL with a full penetrance of the disease. 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 broadly applied targeted agents: ibrutinib and venetoclax. This also opens the door to new targeted agents against R-RAS2 itself, an approach not yet explored in the clinic.<\/jats:p>","DOI":"10.3390\/cancers15245817","type":"journal-article","created":{"date-parts":[[2023,12,12]],"date-time":"2023-12-12T11:30:14Z","timestamp":1702380614000},"page":"5817","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Mice Overexpressing Wild-Type RRAS2 Are a Novel Model for Preclinical Testing of Anti-Chronic Lymphocytic Leukemia Therapies"],"prefix":"10.3390","volume":"15","author":[{"given":"Alejandro M.","family":"Hortal","sequence":"first","affiliation":[{"name":"Immune System Development and Function Program, Centro Biolog\u00eda Molecular Severo Ochoa, Consejo Superior de Investigaciones Cient\u00edficas (CSIC), Universidad Aut\u00f3noma de Madrid, 28049 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Villanueva","sequence":"additional","affiliation":[{"name":"Immune System Development and Function Program, Centro Biolog\u00eda Molecular Severo Ochoa, Consejo Superior de Investigaciones Cient\u00edficas (CSIC), Universidad Aut\u00f3noma de Madrid, 28049 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irene","family":"Arellano","sequence":"additional","affiliation":[{"name":"Immune System Development and Function Program, Centro Biolog\u00eda Molecular Severo Ochoa, Consejo Superior de Investigaciones Cient\u00edficas (CSIC), Universidad Aut\u00f3noma de Madrid, 28049 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Prieto","sequence":"additional","affiliation":[{"name":"Immune System Development and Function Program, Centro Biolog\u00eda Molecular Severo Ochoa, Consejo Superior de Investigaciones Cient\u00edficas (CSIC), Universidad Aut\u00f3noma de Madrid, 28049 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pilar","family":"Mendoza","sequence":"additional","affiliation":[{"name":"Immune System Development and Function Program, Centro Biolog\u00eda Molecular Severo Ochoa, Consejo Superior de Investigaciones Cient\u00edficas (CSIC), Universidad Aut\u00f3noma de Madrid, 28049 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9398-6072","authenticated-orcid":false,"given":"Xos\u00e9 R.","family":"Bustelo","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n del C\u00e1ncer, Instituto de Biolog\u00eda Molecular y Celular del C\u00e1ncer and Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer, Consejo Superior de Investigaciones Cient\u00edficas (CSIC), Universidad de Salamanca, 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Balbino","family":"Alarc\u00f3n","sequence":"additional","affiliation":[{"name":"Immune System Development and Function Program, Centro Biolog\u00eda Molecular Severo Ochoa, Consejo Superior de Investigaciones Cient\u00edficas (CSIC), Universidad Aut\u00f3noma de Madrid, 28049 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1038\/s41571-019-0239-8","article-title":"Chronic Lymphocytic Leukaemia: From Genetics to Treatment","volume":"16","author":"Bosch","year":"2019","journal-title":"Nat. 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