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To try and obtain direct experimental evidence of the specific mechanistic implication of SOS1 in CML development, here, we combined a murine model of CML driven by a p210BCR\/ABL transgene with our tamoxifen-inducible SOS1\/2-KO system in order to investigate the phenotypic impact of the direct genetic ablation of SOS1 or SOS2 on the pathogenesis of CML. Our observations showed that, in contrast to control animals expressing normal levels of SOS1 and SOS2 or to single SOS2-KO mice, p210BCR\/ABL transgenic mice devoid of SOS1 presented significantly extended survival curves and also displayed an almost complete disappearance of the typical hematological alterations and splenomegaly constituting the hallmarks of CML. SOS1 ablation also resulted in a specific reduction in the proliferation and the total number of colony-forming units arising from the population of bone marrow stem\/progenitor cells from p210BCR\/ABL transgenic mice. The specific blockade of CML development caused by SOS1 ablation in p210BCR\/ABL mice indicates that SOS1 is critically required for CML pathogenesis and supports the consideration of this cellular GEF as a novel, alternative bona fide therapeutic target for CML treatment in the clinic.<\/jats:p>","DOI":"10.3390\/cancers14163893","type":"journal-article","created":{"date-parts":[[2022,8,11]],"date-time":"2022-08-11T21:15:05Z","timestamp":1660252505000},"page":"3893","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Critical Requirement of SOS1 for Development of BCR\/ABL-Driven Chronic Myelogenous Leukemia"],"prefix":"10.3390","volume":"14","author":[{"given":"Carmela","family":"G\u00f3mez","sequence":"first","affiliation":[{"name":"Centro de Investigaci\u00f3n del C\u00e1ncer, Instituto de Biolog\u00eda Molecular y Celular del C\u00e1ncer, CSIC-University of Salamanca and CIBERONC, 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8956-3904","authenticated-orcid":false,"given":"R\u00f3sula","family":"Garcia-Navas","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n del C\u00e1ncer, Instituto de Biolog\u00eda Molecular y Celular del C\u00e1ncer, CSIC-University of Salamanca and CIBERONC, 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8110-0991","authenticated-orcid":false,"given":"Fernando C.","family":"Baltan\u00e1s","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n del C\u00e1ncer, Instituto de Biolog\u00eda Molecular y Celular del C\u00e1ncer, CSIC-University of Salamanca and CIBERONC, 37007 Salamanca, Spain"},{"name":"Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Roc\u00edo, CSIC, Universidad de Sevilla, 41013 Seville, Spain"},{"name":"Departamento de Fisiolog\u00eda M\u00e9dica y Biof\u00edsica, Universidad de Sevilla, 41013 Seville, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roc\u00edo","family":"Fuentes-Mateos","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n del C\u00e1ncer, Instituto de Biolog\u00eda Molecular y Celular del C\u00e1ncer, CSIC-University of Salamanca and CIBERONC, 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alberto","family":"Fern\u00e1ndez-Medarde","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n del C\u00e1ncer, Instituto de Biolog\u00eda Molecular y Celular del C\u00e1ncer, CSIC-University of Salamanca and CIBERONC, 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nuria","family":"Calzada","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n del C\u00e1ncer, Instituto de Biolog\u00eda Molecular y Celular del C\u00e1ncer, CSIC-University of Salamanca and CIBERONC, 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3565-0321","authenticated-orcid":false,"given":"Eugenio","family":"Santos","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n del C\u00e1ncer, Instituto de Biolog\u00eda Molecular y Celular del C\u00e1ncer, CSIC-University of Salamanca and CIBERONC, 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,11]]},"reference":[{"key":"ref_1","first-page":"85","article-title":"Chromosome Studies on Normal and Leukemic Human Leukocytes","volume":"25","author":"Nowell","year":"1960","journal-title":"J. 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